rs10077543
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6
The NM_024577.4(SH3TC2):āc.1483A>Gā(p.Thr495Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000973 in 1,613,726 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_024577.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SH3TC2 | NM_024577.4 | c.1483A>G | p.Thr495Ala | missense_variant | 11/17 | ENST00000515425.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SH3TC2 | ENST00000515425.6 | c.1483A>G | p.Thr495Ala | missense_variant | 11/17 | 1 | NM_024577.4 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.000566 AC: 86AN: 151920Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000159 AC: 40AN: 251182Hom.: 0 AF XY: 0.000110 AC XY: 15AN XY: 135794
GnomAD4 exome AF: 0.0000479 AC: 70AN: 1461688Hom.: 0 Cov.: 80 AF XY: 0.0000440 AC XY: 32AN XY: 727136
GnomAD4 genome ? AF: 0.000572 AC: 87AN: 152038Hom.: 0 Cov.: 33 AF XY: 0.000565 AC XY: 42AN XY: 74310
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Sep 28, 2016 | - - |
Charcot-Marie-Tooth disease Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Molecular Genetics Laboratory, London Health Sciences Centre | - | - - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 17, 2021 | The p.T495A variant (also known as c.1483A>G), located in coding exon 11 of the SH3TC2 gene, results from an A to G substitution at nucleotide position 1483. The threonine at codon 495 is replaced by alanine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
SH3TC2-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Feb 17, 2021 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Charcot-Marie-Tooth disease type 4 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 23, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at