rs201877419
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The ENST00000450136.2(TRIM32):c.292C>A(p.Leu98Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000589 in 1,614,038 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
ENST00000450136.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TRIM32 | NM_012210.4 | c.292C>A | p.Leu98Ile | missense_variant | 2/2 | ENST00000450136.2 | NP_036342.2 | |
ASTN2 | NM_001365068.1 | c.2806+27737G>T | intron_variant | ENST00000313400.9 | NP_001351997.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TRIM32 | ENST00000450136.2 | c.292C>A | p.Leu98Ile | missense_variant | 2/2 | 1 | NM_012210.4 | ENSP00000408292 | P1 | |
ASTN2 | ENST00000313400.9 | c.2806+27737G>T | intron_variant | 5 | NM_001365068.1 | ENSP00000314038 | A2 |
Frequencies
GnomAD3 genomes AF: 0.000388 AC: 59AN: 152200Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000104 AC: 26AN: 251172Hom.: 0 AF XY: 0.0000737 AC XY: 10AN XY: 135774
GnomAD4 exome AF: 0.0000246 AC: 36AN: 1461720Hom.: 0 Cov.: 30 AF XY: 0.0000220 AC XY: 16AN XY: 727168
GnomAD4 genome AF: 0.000387 AC: 59AN: 152318Hom.: 0 Cov.: 32 AF XY: 0.000510 AC XY: 38AN XY: 74480
ClinVar
Submissions by phenotype
not provided Uncertain:3
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Feb 20, 2023 | In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously reported as a pathogenic or benign germline variant to our knowledge; This variant is associated with the following publications: (PMID: 27485054) - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jul 11, 2016 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | May 19, 2022 | - - |
Bardet-Biedl syndrome 11 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Feb 16, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
Sarcotubular myopathy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Feb 16, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
Sarcotubular myopathy;C1859569:Bardet-Biedl syndrome 11 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Apr 01, 2022 | - - |
Bardet-Biedl syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 22, 2023 | This sequence change replaces leucine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 98 of the TRIM32 protein (p.Leu98Ile). This variant is present in population databases (rs201877419, gnomAD 0.07%). This variant has not been reported in the literature in individuals affected with TRIM32-related conditions. ClinVar contains an entry for this variant (Variation ID: 289342). 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. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at