# NM_005422.4(TECTA):c.29G>C (p.Trp10Ser)

https://sugi.bio/variant/tecta-p-trp10ser

## Summary

**TECTA p.Trp10Ser (c.29G>C)** is classified **Likely benign** in TECTA (ClinVar, Single submitter, 1 submitter). AlphaMissense: likely benign (0.1578); Very rare (popmax 0.000254%, nfe); Associated with autosomal dominant nonsyndromic hearing loss 12.

**At a glance:** Likely benign · review: Single submitter · rsID rs1591433475 · 1 submitter · 1 linked condition · AlphaMissense likely benign · very rare (popmax 0.000254%, nfe)

## For patients & families {#patients}

This is a change in the TECTA gene that is classified as likely benign — not considered disease-causing, submitted by 1 submitter, and is linked to autosomal dominant nonsyndromic hearing loss 12.

*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:** [Condition overview & support (NIH GARD)](https://rarediseases.info.nih.gov/diseases/0018107/index) · [Find a genetic counselor (NSGC)](https://findageneticcounselor.nsgc.org/).

## Identity {#identity}

| Field | Value |
| --- | --- |
| Gene | [TECTA](https://sugi.bio/atlas/gene/TECTA/) |
| Protein change (HGVS p.) | p.Trp10Ser |
| Coding change (HGVS c.) | c.29G>C |
| MANE Select transcript | [NM_005422](https://www.ncbi.nlm.nih.gov/nuccore/NM_005422) |
| dbSNP | [rs1591433475](https://www.ncbi.nlm.nih.gov/snp/rs1591433475/) |
| Variant type | single nucleotide variant |
| Location | chr11:121102694-121102694 (GRCh38) |
| ClinVar | [VCV689604](https://www.ncbi.nlm.nih.gov/clinvar/variation/689604/) |

**All HGVS expressions:** `NC_000011.10:g.121102694G>C`, `NC_000011.9:g.120973403G>C`, `NG_011633.1:g.5029G>C`, `NM_001378761.1:c.986G>C`, `NM_005422.4:c.29G>C`

## Computational & population evidence {#evidence}

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

- AlphaMissense **likely benign** (0.1578)
- REVEL 0.187 (benign-leaning) — agrees with AlphaMissense
- SaProt LLR -5.661 (tolerated) — agrees with AlphaMissense
- → **In-silico consensus:** AlphaMissense, REVEL and SaProt all call this tolerated
- Conservation: phyloP 9.983, GERP 1.73, phastCons 1 — highly conserved (differs from AlphaMissense)
- CADD: **PHRED 24.9**. 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.*
- Regional missense constraint: **o/e 0.93** across the covering region of the MANE Select transcript (121,102,666–121,168,849), spanning 66,183 bp. Chi-square p 0.00019. Describes the region, not this allele; gnomAD v4.1.1's own constrained determination. *Descriptive; no ACMG code applied.*
- SpliceAI: **below the reporting threshold**. This position is scored for a different substitution (G>A, Δ0.44 acceptor loss), so this allele was evaluated and its deltas all fell under Δ0.2 — a prediction of no splicing effect for this allele, not a gap in our data. *No ACMG code assigned.*
- Population frequency (gnomAD v4.1): grpmax **0.000254%** (nfe) · FAF95 6.8e-05% · FAF99 1.9e-05% · 3/1,179,684 in the highest group · 3/1,613,576 alleles overall — very rare (popmax 0.000254%, nfe).

*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}

**TECTA** population constraint: LOEUF 0.661, pLI 1.9954e-20, missense-Z 2.4637. *Lower LOEUF and higher pLI indicate a gene that tolerates loss-of-function poorly; ClinGen dosage is the curated haploinsufficiency call.*

Curated gene–disease validity (ClinGen):

- **nonsyndromic genetic hearing loss** — Definitive (AR)
- **nonsyndromic genetic hearing loss** — Definitive (AD)

## Protein context {#protein}


AlphaFold model confidence (whole protein): pLDDT 77.64, 19% of residues very-high.

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

*Describes the biological roles of TECTA (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.*


### Pathways affected {#pathways}

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

| Pathway (Reactome) | Evidence |
| --- | --- |
| [Post-translational modification: synthesis of GPI-anchored proteins](https://reactome.org/content/detail/R-HSA-163125) | curated |

## Clinical significance {#significance}

**Likely benign** — review status Single submitter *(criteria provided, single submitter)*.

**Submitter consensus:** unanimous (1/1 Likely benign).

### Submitter classifications {#submitters}

| Submitter | Classification | Review | Method | Date |
| --- | --- | --- | --- | --- |
| Genetic Testing Center for Deafness, Department of Otolaryngology Head & Neck Surgery, Institute of Otolaryngology, Chinese PLA General Hospital | Likely benign | criteria provided, single submitter | case-control |  |

## Associated conditions {#conditions}

[autosomal dominant nonsyndromic hearing loss 12](https://sugi.bio/atlas/disease/autosomal-dominant-nonsyndromic-hearing-loss-12/).

**Reported phenotype names (ClinVar):** Autosomal dominant nonsyndromic hearing loss 12, DEAFNESS, AUTOSOMAL DOMINANT 8.

## Similar variants {#similar}

Related TECTA variant pages (same residue, condition, or type): [TECTA p.Arg371Gly](/variant/tecta-p-arg371gly), [TECTA c.4690-1G>A](/variant/tecta-c-4690-minus-1g-a), [TECTA p.Ala567Thr](/variant/tecta-p-ala567thr), [TECTA p.Arg284Cys](/variant/tecta-p-arg284cys), [TECTA p.Arg474Cys](/variant/tecta-p-arg474cys), [TECTA p.Cys1072=](/variant/tecta-p-cys1072), [TECTA p.Cys1402Ser](/variant/tecta-p-cys1402ser), [TECTA p.Cys294Arg](/variant/tecta-p-cys294arg).

### 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 689604). 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.*