# NM_019023.5(PRMT7):c.1951TTC[1] (p.Phe652del)

https://sugi.bio/variant/prmt7-p-phe652del

## Summary

**PRMT7 p.Phe652del (c.1951TTC[1])** is classified **Conflicting classifications of pathogenicity** in PRMT7 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-11-23). Rare (popmax 0.249%, amr).

**At a glance:** Conflicting classifications of pathogenicity · review: Conflicting submitters · rsID rs562766169 · 4 submitters · rare (popmax 0.249%, amr)

## For patients & families {#patients}

This is a change in the PRMT7 gene that is of uncertain or conflicting significance (submitters disagree on it), submitted by 4 submitters.

*Reference information, not medical advice, and not a prediction for any individual. A genetic counselor or clinician can interpret what it means for you and your family.*

**Support & next steps:** [Find a genetic counselor (NSGC)](https://findageneticcounselor.nsgc.org/).

## Identity {#identity}

| Field | Value |
| --- | --- |
| Gene | [PRMT7](https://sugi.bio/atlas/gene/PRMT7/) |
| Protein change (HGVS p.) | p.Phe652del |
| Coding change (HGVS c.) | c.1951TTC[1] |
| MANE Select transcript | [NM_019023](https://www.ncbi.nlm.nih.gov/nuccore/NM_019023) |
| dbSNP | [rs562766169](https://www.ncbi.nlm.nih.gov/snp/rs562766169/) |
| Variant type | Microsatellite |
| Location | chr16:68357095-68357097 (GRCh38) |
| ClinVar | [VCV712115](https://www.ncbi.nlm.nih.gov/clinvar/variation/712115/) |

**All HGVS expressions:** `NC_000016.10:g.68357096TTC[1]`, `NC_000016.9:g.68390999TTC[1]`, `NG_054896.1:g.51123TTC[1]`, `NM_001184824.4:c.1801TTC[1]`, `NM_001290018.2:c.1951TTC[1]`, `NM_001351143.3:c.1951TTC[1]`, `NM_001351144.3:c.1954TTC[1]`, `NM_001378018.1:c.1951TTC[1]`, `NM_001378020.1:c.1744TTC[1]`, `NM_001378021.1:c.1714TTC[1]`, `NM_001378022.1:c.1714TTC[1]`, `NM_001378023.1:c.1714TTC[1]`, `NM_019023.2:c.1954_1956delTTC`, `NM_019023.3:c.1954_1956del`, `NM_019023.5:c.1951TTC[1]`, `NR_147056.3:n.2212TTC[1]`, `NR_147057.3:n.2772TTC[1]`, `NR_147058.3:n.2347TTC[1]`, `NR_165365.1:n.3294TTC[1]`, `NR_165366.1:n.3070TTC[1]`, `NR_165367.1:n.2973TTC[1]`, `NR_165368.1:n.3071TTC[1]`, `NR_165369.1:n.2936TTC[1]`, `NR_165370.1:n.2503TTC[1]`, `NR_165371.1:n.2999TTC[1]`, `NR_165372.1:n.2325TTC[1]`, `NR_165373.1:n.2310TTC[1]`

## Computational & population evidence {#evidence}

**Concordance:** Mixed / partial computational evidence (see below).

- **Missense predictors (AlphaMissense/REVEL/SaProt) do not apply** to this variant type — they score amino-acid substitutions only. For non-missense variants the computational signal comes from conservation (below), not from a missing predictor score.
- Conservation: phyloP 11.223, GERP 2.58, phastCons 1 — highly conserved position (PP3-type support)
- Molecular consequence: **in-frame indel**.
- CADD: **PHRED 15.45**. No single ClinGen-calibrated threshold exists and the expert panels that use CADD disagree — GUCY2D/AIPL1 require ≥ 20.0 for an untranslated-region variant, ABCA4 ≥ 28.1 for a synonymous or indel variant, the Pulmonary Hypertension panel imports Pejaver 2022's missense-calibrated numbers, and the Antibody Deficiencies panel declines CADD entirely for PIK3CD. CADD v1.7 also incorporates Zoonomia phyloP, so it partly re-expresses the conservation above. *Descriptive; no threshold applied.*
- SpliceAI: **not assessed** — the release is built from a substitutions-only source, so it holds no microsatellite variants. That is a property of the dataset, not of the variant, and is not evidence against a splicing effect.
- Population frequency (gnomAD v4.1): grpmax **0.249%** (amr) · FAF95 0.216% · FAF99 0.204% · 149/59,896 in the highest group · 1,897/1,613,212 alleles overall — rare (popmax 0.249%, amr).

| Ancestry group | Allele frequency | 1 in |
| --- | --- | --- |
| Admixed American (grpmax) | 0.249% | 402 |
| European (non-Finnish) | 0.141% | 708 |
| Remaining individuals (not grpmax-eligible) | 0.0896% | 1,115 |
| African / African-American | 0.028% | 3,572 |
| Finnish (not grpmax-eligible) | 0.00314% | 31,868 |
| South Asian | 0.0022% | 45,507 |

*Computational predictors are not independent (ClinGen Variant Classification guidance): AlphaMissense (Cheng et al. 2023) carries the ACMG weight for missense and conservation (phyloP/GERP/phastCons) for non-missense; REVEL (Pejaver-2022 calibrated strength bands) and SaProt (Su et al. 2023, structure-aware, ClinVar-independent protein language model, raw LLR) are shown as orthogonal agreement signals, not additive. For frequency, the gnomAD v4.1 grpmax filtering allele frequency (FAF95) is ClinGen's designated BA1/BS1 input (gnomAD v4 guidance v3.0, June 2025); BA1/BS1 thresholds are disease-specific, not a blanket 5%. Predictions, not a clinical determination.*

## Gene constraint & dosage {#gene-context}

**PRMT7** population constraint: LOEUF 1.01, pLI 1.7205e-16, missense-Z 0.65479. *Lower LOEUF and higher pLI indicate a gene that tolerates loss-of-function poorly; ClinGen dosage is the curated haploinsufficiency call.*

## Protein context {#protein}

Residue **652** lies in the sam-dependent mtase prmt-type 2 domain.

AlphaFold model confidence (whole protein): pLDDT 93.19, 83% of residues very-high.

## What this gene does {#gene-function}

*Describes the biological roles of PRMT7 (the gene this variant disrupts) — not effects measured for this specific variant. A damaging variant is expected to affect these functions and pathways; the degree depends on the variant.*

**How this variant is thought to act:** PRMT7's established molecular role includes S-adenosylmethionine-dependent methyltransferase activity. p.Phe652del falls in the sam-dependent mtase prmt-type 2 domain.


### Pathways affected {#pathways}

PRMT7 participates in **1 Reactome pathway** (⚕ = disease pathway):

| Pathway (Reactome) | Evidence |
| --- | --- |
| [RMTs methylate histone arginines](https://reactome.org/content/detail/R-HSA-3214858) | curated |

### Molecular function & processes (GO — experimentally supported) {#go}

**Molecular function:** S-adenosylmethionine-dependent methyltransferase activity, protein-arginine omega-N monomethyltransferase activity, protein-arginine omega-N symmetric methyltransferase activity, histone binding, ribonucleoprotein complex binding, histone H4 methyltransferase activity.

**Biological process:** spliceosomal snRNP assembly, peptidyl-arginine methylation.

## Clinical significance {#significance}

**Conflicting classifications of pathogenicity** — review status Conflicting submitters *(criteria provided, conflicting classifications)*, last evaluated 2025-11-23.

**Submitter consensus:** conflicting (2 Uncertain significance, 2 Likely benign).

**Submission history:** 4 submissions (2022–2025); classifications have differed over time.

### Submitter classifications {#submitters}

| Submitter | Classification | Review | Method | Date |
| --- | --- | --- | --- | --- |
| Genetic Services Laboratory, University of Chicago | Uncertain significance | no assertion criteria provided | clinical testing | 2022-09-03 |
| GeneDx | Uncertain significance | criteria provided, single submitter | clinical testing | 2023-10-14 |
| PreventionGenetics, part of Exact Sciences | Likely benign | no assertion criteria provided | clinical testing | 2022-04-28 |
| Labcorp Genetics (formerly Invitae), Labcorp | Likely benign | criteria provided, single submitter | clinical testing | 2025-11-23 |

**Reported phenotype names (ClinVar):** not provided, not specified, PRMT7-related disorder, PRMT7-related condition, none provided, AllHighlyPenetrant.

## Similar variants {#similar}

Related PRMT7 variant pages (same residue, condition, or type): [PRMT7 p.Arg358fs](/variant/prmt7-p-arg358fs), [PRMT7 p.Glu144fs](/variant/prmt7-p-glu144fs), [PRMT7 p.Leu475fs](/variant/prmt7-p-leu475fs), [PRMT7 p.Gly76_Leu77insThrGly](/variant/prmt7-p-gly76-leu77insthrgly), [PRMT7 p.Leu476del](/variant/prmt7-p-leu476del), [PRMT7 c.132+22_132+24del](/variant/prmt7-c-132-plus-22-132-plus-24del), [PRMT7 c.1323+12TTG[2]](/variant/prmt7-c-1323-plus-12ttg-2), [PRMT7 c.1909-9_1909-7del](/variant/prmt7-c-1909-minus-9-1909-minus-7del).

### Data sources & attribution {#sources}

ClinVar (NCBI — public domain, built 2026-10-14); gnomAD v4.1 (Broad Institute, built 2026-10-14); AlphaMissense (Cheng et al. 2023, © Google DeepMind — CC BY 4.0, built 2026-01-27); REVEL (Ioannidis et al. 2016 — ODbL, built 2026-07-13); SaProt (Su et al. 2023 — MIT, built 2026-10-14); SpliceAI (Illumina — free for non-commercial use, built 2026-10-13); CADD (Rentzsch et al. 2019, University of Washington — free for non-commercial use, built 2026-10-10); Conservation (phyloP/phastCons/GERP) (UCSC hg38 470-way mammal (Hiller Lab) + Ensembl Compara, built 2026-07-12); gnomAD Non-coding Constraint (Gnocchi) (Chen et al. 2024, Broad Institute — CC0, built 2026-10-11); gnomAD Regional Missense Constraint (Broad Institute — CC0, built 2026-10-13); Pangolin (Zeng & Li 2022 — CC BY 4.0, built 2026-10-11); Repeat regions (UCSC — RepeatMasker, TRF, segmental duplications, built 2026-10-11); ClinGen (ClinGen, built 2026-09-22); UniProt (CC BY 4.0); Reactome / GO (CC BY 4.0, built 2026-09-23); MaveDB (per-record license, built 2026-10-11); CIViC (CC0, built 2026-09-22); Orphanet (Orphanet, built 2026-06-12)

*Primary record: NCBI ClinVar (variation 712115). Classifications reflect these databases as of the page's build date and may change. Free reference use — not medical advice; consult the primary submitters and a clinician.*