rs111033571
Variant summary
Our verdict is Likely pathogenic. Variant got 9 ACMG points: 10P and 1B. PM2PP5_Very_StrongBP4
The NM_012210.4(TRIM32):c.388C>T(p.Pro130Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000031 in 1,613,984 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P130L) has been classified as Uncertain significance.
Frequency
Consequence
NM_012210.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TRIM32 | NM_012210.4 | c.388C>T | p.Pro130Ser | missense_variant | 2/2 | ENST00000450136.2 | |
ASTN2 | NM_001365068.1 | c.2806+27641G>A | intron_variant | ENST00000313400.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TRIM32 | ENST00000450136.2 | c.388C>T | p.Pro130Ser | missense_variant | 2/2 | 1 | NM_012210.4 | P1 | |
ASTN2 | ENST00000313400.9 | c.2806+27641G>A | intron_variant | 5 | NM_001365068.1 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152156Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000799 AC: 2AN: 250324Hom.: 0 AF XY: 0.00000738 AC XY: 1AN XY: 135552
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461828Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1AN XY: 727228
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152156Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74316
ClinVar
Submissions by phenotype
Bardet-Biedl syndrome 11 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Feb 01, 2008 | - - |
TRIM32-related disorder Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Nov 22, 2023 | The TRIM32 c.388C>T variant is predicted to result in the amino acid substitution p.Pro130Ser. In a consanguineous family, this variant was reported in the homozygous state in multiple individuals with Bardet-Biedl syndrome (Chiang et al. 2006. PubMed ID: 16606853). Zebrafish studies suggest this variant may affect protein function (Chiang et al. 2006. PubMed ID: 16606853; Zaghloul et al. 2010. PubMed ID: 20498079). This variant is reported in 0.0028% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/9-119460409-C-T). This variant is interpreted as likely pathogenic. - |
not provided Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Feb 21, 2023 | - - |
Bardet-Biedl syndrome Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Dec 12, 2023 | This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 130 of the TRIM32 protein (p.Pro130Ser). This variant is present in population databases (rs111033571, gnomAD 0.002%). This missense change has been observed in individual(s) with Bardet–Biedl syndrome (PMID: 16606853). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 7351). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. Experimental studies have shown that this missense change affects TRIM32 function (PMID: 16606853). For these reasons, this variant has been classified as Pathogenic. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at