# NM_020831.6(MRTFA):c.2693_2711del (p.Pro898fs)

https://sugi.bio/variant/mrtfa-p-pro898fs

## Summary

**MRTFA p.Pro898fs (c.2693_2711del)** is classified **Uncertain significance** in MRTFA (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-13). No gnomAD frequency available for this variant.

**At a glance:** Uncertain significance · review: Single submitter · rsID rs2517787339 · 1 submitter · no gnomAD frequency available for this variant

## For patients & families {#patients}

This is a change in the MRTFA gene that is currently of uncertain significance — a definitive interpretation has not yet been established, submitted by 1 submitter.

*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 | [MRTFA](https://sugi.bio/atlas/gene/MRTFA/) |
| Protein change (HGVS p.) | p.Pro898fs |
| Coding change (HGVS c.) | c.2693_2711del |
| MANE Select transcript | [NM_020831](https://www.ncbi.nlm.nih.gov/nuccore/NM_020831) |
| dbSNP | [rs2517787339](https://www.ncbi.nlm.nih.gov/snp/rs2517787339/) |
| Variant type | Deletion |
| Location | chr22:40411775-40411793 (GRCh38) |
| ClinVar | [VCV2030248](https://www.ncbi.nlm.nih.gov/clinvar/variation/2030248/) |

**All HGVS expressions:** `LRG_1427:g.229927_229945del`, `LRG_1427t1:c.2693_2711del`, `LRG_1427t2:c.2498_2516del`, `NC_000022.10:g.40807783_40807801del`, `NC_000022.11:g.40411779_40411797del`, `NG_065810.1:g.229927_229945del`, `NM_001282660.2:c.2393_2411del`, `NM_001282661.3:c.2543_2561del`, `NM_001282662.3:c.*6_*24del`, `NM_001318139.2:c.2498_2516del`, `NM_020831.6:c.2693_2711del`

## 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 -7.085, GERP -4.19 — fast-evolving / accelerated position
- Molecular consequence: **frameshift** — a predicted loss-of-function variant. the gene is **loss-of-function-intolerant** (LOEUF 0.389, pLI 0.99999), supporting a loss-of-function disease mechanism. *Descriptive; not an applied PVS1 code.*
- Nonsense-mediated decay: the premature termination codon is **in the last exon (15 of 15)** — predicted to **escape NMD**, so the truncated protein is likely expressed. An input to PVS1, not an applied code.
- SpliceAI: **not assessed** — the release is built from a substitutions-only source, so it holds no deletion variants. That is a property of the dataset, not of the variant, and is not evidence against a splicing effect.
- Population frequency: **no gnomAD frequency available for this variant** — rarity (ACMG PM2) and BA1/BS1 cannot be assessed for this variant.

*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}

**MRTFA** population constraint: LOEUF 0.389, pLI 0.99999, missense-Z -0.061525. *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 **898** lies in a UniProt-annotated variant site (in imd66; probable loss-of-function; patient's dendritic cells are morphologically distinct from control dendritic cells and show reduced spreading on fibronectin-coated coverslips, a marked reduction in total f-actin staining and a complete absence of podosomes, a similar phenotype to that of thp1 cells in which mrtfa was silenced).

AlphaFold model confidence (whole protein): pLDDT 56.59, 19% of residues very-high.

**2 experimental structure(s)** (PDB): [2KVU](https://www.rcsb.org/structure/2KVU), [2KW9](https://www.rcsb.org/structure/2KW9).

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

*Describes the biological roles of MRTFA (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:** MRTFA's established molecular role includes transcription coactivator activity.


### Pathways affected {#pathways}

MRTFA participates in **2 Reactome pathways** (⚕ = disease pathway):

| Pathway (Reactome) | Evidence |
| --- | --- |
| [RHO GTPases Activate Formins](https://reactome.org/content/detail/R-HSA-5663220) | curated |
| [SUMOylation of transcription cofactors](https://reactome.org/content/detail/R-HSA-3899300) | curated |

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

**Molecular function:** transcription coactivator activity, actin binding, leucine zipper domain binding.

**Biological process:** wound healing, spreading of cells, positive regulation of transcription by RNA polymerase II, smooth muscle cell differentiation, positive regulation of miRNA transcription.

## Clinical significance {#significance}

**Uncertain significance** — review status Single submitter *(criteria provided, single submitter)*, last evaluated 2022-09-13.

**Submitter consensus:** unanimous (1/1 Uncertain significance).

### Submitter classifications {#submitters}

| Submitter | Classification | Review | Method | Date |
| --- | --- | --- | --- | --- |
| Labcorp Genetics (formerly Invitae), Labcorp | Uncertain significance | criteria provided, single submitter | clinical testing | 2022-09-13 |

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

## Similar variants {#similar}

Related MRTFA variant pages (same residue, condition, or type): [MRTFA p.Pro898Ser](/variant/mrtfa-p-pro898ser), [MRTFA p.Pro898Leu](/variant/mrtfa-p-pro898leu), [MRTFA c.2518-15del](/variant/mrtfa-c-2518-minus-15del), [MRTFA c.2365-26_2365-19del](/variant/mrtfa-c-2365-minus-26-2365-minus-19del), [MRTFA p.Ala523_Val531del](/variant/mrtfa-p-ala523-val531del), [MRTFA p.Glu658del](/variant/mrtfa-p-glu658del), [MRTFA p.Glu678del](/variant/mrtfa-p-glu678del), [MRTFA p.Glu875del](/variant/mrtfa-p-glu875del).

### Data sources & attribution {#sources}

ClinVar (NCBI — public domain, built 2026-10-14); gnomAD v4.1 (Broad Institute, built 2026-10-15); 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 2030248). 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.*