rs551953142
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM1PM2PP3
The ENST00000515425.6(SH3TC2):āc.1654G>Cā(p.Glu552Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000178 in 1,461,766 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E552K) has been classified as Uncertain significance.
Frequency
Consequence
ENST00000515425.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SH3TC2 | NM_024577.4 | c.1654G>C | p.Glu552Gln | missense_variant | 11/17 | ENST00000515425.6 | NP_078853.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SH3TC2 | ENST00000515425.6 | c.1654G>C | p.Glu552Gln | missense_variant | 11/17 | 1 | NM_024577.4 | ENSP00000423660 | P2 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome AF: 0.0000178 AC: 26AN: 1461766Hom.: 0 Cov.: 33 AF XY: 0.0000165 AC XY: 12AN XY: 727166
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Distal spinal muscular atrophy Uncertain:1
Uncertain significance, no assertion criteria provided | research | Genesis Genome Database | Aug 14, 2019 | - - |
Charcot-Marie-Tooth disease type 4 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Aug 09, 2022 | 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. 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 expected to disrupt SH3TC2 protein function. ClinVar contains an entry for this variant (Variation ID: 543343). This variant has not been reported in the literature in individuals affected with SH3TC2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamic acid, which is acidic and polar, with glutamine, which is neutral and polar, at codon 552 of the SH3TC2 protein (p.Glu552Gln). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at