# NM_001353214.3(DYM):c.1717C>T (p.Leu573=)

https://sugi.bio/variant/dym-p-leu573

## Summary

**DYM p.Leu573= (c.1717C>T)** is classified **Benign/Likely benign** in DYM (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-01). Rare (popmax 0.248%, mid).

**At a glance:** Benign/Likely benign · review: Multiple submitters · rsID rs145279594 · 5 submitters · rare (popmax 0.248%, mid)

## For patients & families {#patients}

This is a change in the DYM gene that is classified as benign/likely benign — not considered disease-causing, submitted by 5 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 | [DYM](https://sugi.bio/atlas/gene/DYM/) |
| Protein change (HGVS p.) | p.Leu573= |
| Coding change (HGVS c.) | c.1717C>T |
| MANE Select transcript | [NM_001353214](https://www.ncbi.nlm.nih.gov/nuccore/NM_001353214) |
| dbSNP | [rs145279594](https://www.ncbi.nlm.nih.gov/snp/rs145279594/) |
| Variant type | single nucleotide variant |
| Location | chr18:49163696-49163696 (GRCh38) |
| ClinVar | [VCV283838](https://www.ncbi.nlm.nih.gov/clinvar/variation/283838/) |

**All HGVS expressions:** `NC_000018.10:g.49163696G>A`, `NC_000018.9:g.46690066G>A`, `NG_009239.2:g.302038C>T`, `NM_001353210.3:c.1549C>T`, `NM_001353211.3:c.1549C>T`, `NM_001353212.3:c.1714C>T`, `NM_001353213.3:c.1714C>T`, `NM_001353214.3:c.1717C>T`, `NM_001353215.3:c.1717C>T`, `NM_001353216.3:c.1552C>T`, `NM_001374428.1:c.1717C>T`, `NM_001374429.1:c.1711C>T`, `NM_001374430.1:c.1717C>T`, `NM_001374431.1:c.1717C>T`, `NM_001374432.1:c.1591C>T`, `NM_001374433.1:c.1552C>T`, `NM_001374434.1:c.1552C>T`, `NM_001374435.1:c.1549C>T`, `NM_001374436.1:c.1426C>T`, `NM_001374437.1:c.1369C>T`, `NM_001374438.1:c.1549C>T`, `NM_001374439.1:c.1546C>T`, `NM_001374440.1:c.1324C>T`, `NM_001374441.1:c.1147C>T`, `NM_001374442.1:c.982C>T`, `NM_001374443.1:c.979C>T`, `NM_001374444.1:c.982C>T`, `NM_017653.6:c.1552C>T`

## 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 and, for splice-region changes, SpliceAI (below), not from a missing predictor score.
- SpliceAI predicts **donor loss** (Δ 0.23) — a splice-altering prediction the current classification does not reflect
- Conservation: phyloP 6.431, GERP 0.912, phastCons 1 — highly conserved position (PP3-type support)
- CADD: **PHRED 7.371**. 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 deltas (raw): acceptor loss **0.00**, donor loss **0.23**, acceptor gain **0.00**, donor gain **0.00**. Largest is donor loss.
- SpliceAI deltas (masked): acceptor loss **0.00**, donor loss **0.23**, acceptor gain **0.00**, donor gain **0.00**.
- Population frequency (gnomAD v4.1): grpmax **0.248%** (mid) · FAF95 0.204% · FAF99 0.201% · 15/6,054 in the highest group · 3,000/1,610,362 alleles overall — rare (popmax 0.248%, mid).

| Ancestry group | Allele frequency | 1 in |
| --- | --- | --- |
| Finnish (not grpmax-eligible) | 0.249% | 402 |
| Middle Eastern (grpmax) | 0.248% | 404 |
| Ashkenazi Jewish (not grpmax-eligible) | 0.247% | 404 |
| European (non-Finnish) | 0.211% | 474 |
| Remaining individuals (not grpmax-eligible) | 0.207% | 483 |
| Admixed American | 0.195% | 512 |
| African / African-American | 0.0307% | 3,257 |

Finnish shows a higher raw frequency than the grpmax group. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and "Remaining individuals" — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

*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}

**DYM** population constraint: LOEUF 1.081, pLI 7.9636e-21, missense-Z 0.92126; ClinGen dosage — haploinsufficiency 30, triplosensitivity 0 (0–3 scale). *Lower LOEUF and higher pLI indicate a gene that tolerates loss-of-function poorly; ClinGen dosage is the curated haploinsufficiency call.*

## Protein context {#protein}


AlphaFold model confidence (whole protein): pLDDT 87.91, 72% of residues very-high.

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

*Describes the biological roles of DYM (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:** DYM's established molecular role includes enzyme binding.


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

**Molecular function:** enzyme binding.

**Biological process:** Golgi organization, bone development.

## Clinical significance {#significance}

**Benign/Likely benign** — review status Multiple submitters *(criteria provided, multiple submitters, no conflicts)*, last evaluated 2026-02-01.

**Submitter consensus:** conflicting (4 Likely benign, 1 Benign).

**Submission history:** 5 submissions (2015–2026); classifications have differed over time.

### Submitter classifications {#submitters}

| Submitter | Classification | Review | Method | Date |
| --- | --- | --- | --- | --- |
| Blueprint Genetics | Likely benign | criteria provided, single submitter | clinical testing | 2024-10-30 |
| ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Likely benign | criteria provided, single submitter | clinical testing | 2023-10-14 |
| Eurofins Ntd Llc (ga) | Likely benign | criteria provided, single submitter | clinical testing | 2015-10-26 |
| Labcorp Genetics (formerly Invitae), Labcorp | Benign | criteria provided, single submitter | clinical testing | 2026-02-01 |
| CeGaT Center for Human Genetics Tuebingen | Likely benign | criteria provided, single submitter | clinical testing | 2024-06-01 |

**Reported phenotype names (ClinVar):** not specified, not provided, AllHighlyPenetrant, none provided.

## Similar variants {#similar}

Related DYM variant pages (same residue, condition, or type): [DYM c.1728+2T>C](/variant/dym-c-1728-plus-2t-c), [DYM c.947-2A>G](/variant/dym-c-947-minus-2a-g), [DYM p.Arg204Ter](/variant/dym-p-arg204ter), [DYM p.Arg428Ter](/variant/dym-p-arg428ter), [DYM p.Arg588Ter](/variant/dym-p-arg588ter), [DYM p.Arg70Ter](/variant/dym-p-arg70ter), [DYM p.Gln306Ter](/variant/dym-p-gln306ter), [DYM p.Glu87Lys](/variant/dym-p-glu87lys).

### Data sources & attribution {#sources}

ClinVar (NCBI — public domain, built 2026-10-11); gnomAD v4.1 (Broad Institute, built 2026-10-06); 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 2026-07-14); 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 283838). 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.*