5-149012639-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_024577.4(SH3TC2):c.3149C>T(p.Ala1050Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000242 in 1,614,106 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 (★★). Synonymous variant affecting the same amino acid position (i.e. A1050A) has been classified as Likely benign.
Frequency
Consequence
NM_024577.4 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 |
---|---|---|---|---|---|---|---|
SH3TC2 | NM_024577.4 | c.3149C>T | p.Ala1050Val | missense_variant | 13/17 | ENST00000515425.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SH3TC2 | ENST00000515425.6 | c.3149C>T | p.Ala1050Val | missense_variant | 13/17 | 1 | NM_024577.4 | P2 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152104Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000239 AC: 6AN: 251224Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135774
GnomAD4 exome AF: 0.0000246 AC: 36AN: 1461884Hom.: 0 Cov.: 32 AF XY: 0.0000261 AC XY: 19AN XY: 727240
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152222Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74412
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 04, 2022 | The p.A1050V variant (also known as c.3149C>T), located in coding exon 13 of the SH3TC2 gene, results from a C to T substitution at nucleotide position 3149. The alanine at codon 1050 is replaced by valine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species; however, valine is the reference amino acid in other vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Charcot-Marie-Tooth disease type 4 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 24, 2022 | This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1050 of the SH3TC2 protein (p.Ala1050Val). This variant is present in population databases (rs570067509, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with SH3TC2-related conditions. ClinVar contains an entry for this variant (Variation ID: 476905). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt SH3TC2 protein function. 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