# NM_012210.4(TRIM32):c.1263C>T (p.Phe421=)

https://sugi.bio/variant/trim32-p-phe421

## Summary

**TRIM32 p.Phe421= (c.1263C>T)** is classified **Likely benign** in TRIM32 (ClinVar, Single submitter, 2 submitters; last evaluated 2023-04-07). Absent from gnomAD v4.1; Associated with Bardet-Biedl syndrome.

**At a glance:** Likely benign · review: Single submitter · rsID rs2491065979 · 2 submitters · 1 linked condition · absent from gnomAD v4.1

## For patients & families {#patients}

This is a change in the TRIM32 gene that is classified as likely benign — not considered disease-causing, submitted by 2 submitters, and is linked to Bardet-Biedl syndrome.

*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.*

|  |  |
| --- | --- |
| Typical inheritance (of this condition) | Autosomal recessive, Oligogenic |
| Age of onset (of this condition) | Antenatal, Childhood, Infancy, Neonatal |
| Prevalence | 1-9 / 100 000 (Specific population) |
| Clinical trials | 18 registered for this condition — see ClinicalTrials.gov |

**Commonly reported features of Bardet-Biedl syndrome** (across patients with this condition; presentation varies — frequencies from Orphanet):

- Retinal dystrophy — Obligate (100%)
- Cone/cone-rod dystrophy — Very frequent (99-80%)
- Obesity — Very frequent (99-80%)
- Childhood-onset truncal obesity — Very frequent (99-80%)
- Neurodevelopmental delay — Very frequent (99-80%)
- Abnormality of the genitourinary system — Frequent (79-30%)
- Hypogonadism — Frequent (79-30%)
- Abnormal oral cavity morphology — Frequent (79-30%)

**Support & next steps:** [Condition overview & support (NIH GARD)](https://rarediseases.info.nih.gov/diseases/0006866/index) · [Find a genetic counselor (NSGC)](https://findageneticcounselor.nsgc.org/).

## Identity {#identity}

| Field | Value |
| --- | --- |
| Gene | [TRIM32](https://sugi.bio/atlas/gene/TRIM32/) |
| Protein change (HGVS p.) | p.Phe421= |
| Coding change (HGVS c.) | c.1263C>T |
| MANE Select transcript | [NM_012210](https://www.ncbi.nlm.nih.gov/nuccore/NM_012210) |
| dbSNP | [rs2491065979](https://www.ncbi.nlm.nih.gov/snp/rs2491065979/) |
| Variant type | single nucleotide variant |
| Location | chr9:116699005-116699005 (GRCh38) |
| ClinVar | [VCV2999629](https://www.ncbi.nlm.nih.gov/clinvar/variation/2999629/) |

**All HGVS expressions:** `LRG_211:g.16704C>T`, `LRG_211t1:c.1263C>T`, `NC_000009.11:g.119461284C>T`, `NC_000009.12:g.116699005C>T`, `NG_011619.1:g.16704C>T`, `NG_021409.2:g.721053G>A`, `NM_001099679.2:c.1263C>T`, `NM_001365068.1:c.2806+26766G>A`, `NM_001365069.1:c.2794+26766G>A`, `NM_001379048.1:c.1263C>T`, `NM_001379049.1:c.1263C>T`, `NM_001379050.1:c.1263C>T`, `NM_012210.4:c.1263C>T`, `NM_014010.5:c.2653+26766G>A`

## 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 0.135, phastCons 0.932 — weakly conserved position
- CADD: **PHRED 5.391**. 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 looked up on this page** — it was served without the gene's SpliceAI index, so no lookup was made. This is a gap in this page, not in the data, and says nothing about whether a splicing effect is predicted.
- Population frequency: **absent from gnomAD v4.1** — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

*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.*

## Clinical significance {#significance}

**Likely benign** — review status Single submitter *(criteria provided, single submitter)*, last evaluated 2023-04-07.

**Submitter consensus:** unanimous (2/2 Likely benign).

**Submission history:** 2 submissions (2022–2023); classifications have been stable.

### Submitter classifications {#submitters}

| Submitter | Classification | Review | Method | Date |
| --- | --- | --- | --- | --- |
| PreventionGenetics, part of Exact Sciences | Likely benign | no assertion criteria provided | clinical testing | 2022-10-18 |
| Labcorp Genetics (formerly Invitae), Labcorp | Likely benign | criteria provided, single submitter | clinical testing | 2023-04-07 |

## Associated conditions {#conditions}

[Bardet-Biedl syndrome](https://sugi.bio/atlas/disease/bardet-biedl-syndrome/).

**Reported phenotype names (ClinVar):** Bardet-Biedl syndrome, TRIM32-related disorder, TRIM32-related condition.

### Data sources & attribution {#sources}

ClinVar (NCBI — public domain, built 2026-10-14); 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 2026-10-14); 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 2999629). 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.*