rs752016708
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_012210.4(TRIM32):c.496C>T(p.Arg166Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000967 in 1,613,938 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R166Q) has been classified as Uncertain significance.
Frequency
Consequence
NM_012210.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TRIM32 | NM_012210.4 | c.496C>T | p.Arg166Trp | missense_variant | 2/2 | ENST00000450136.2 | |
ASTN2 | NM_001365068.1 | c.2806+27533G>A | intron_variant | ENST00000313400.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TRIM32 | ENST00000450136.2 | c.496C>T | p.Arg166Trp | missense_variant | 2/2 | 1 | NM_012210.4 | P1 | |
ASTN2 | ENST00000313400.9 | c.2806+27533G>A | intron_variant | 5 | NM_001365068.1 | A2 |
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152066Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000398 AC: 10AN: 251188Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135840
GnomAD4 exome AF: 0.000103 AC: 151AN: 1461872Hom.: 0 Cov.: 30 AF XY: 0.0000976 AC XY: 71AN XY: 727240
GnomAD4 genome AF: 0.0000329 AC: 5AN: 152066Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74266
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Sep 27, 2021 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | May 23, 2017 | - - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 21, 2023 | The c.496C>T (p.R166W) alteration is located in exon 2 (coding exon 1) of the TRIM32 gene. This alteration results from a C to T substitution at nucleotide position 496, causing the arginine (R) at amino acid position 166 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Sarcotubular myopathy;C1859569:Bardet-Biedl syndrome 11 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Mar 16, 2022 | - - |
Bardet-Biedl syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 24, 2022 | This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 166 of the TRIM32 protein (p.Arg166Trp). This variant is present in population databases (rs752016708, gnomAD 0.007%). 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: 502143). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. 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