X-19537725-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.
The NM_031892.3(SH3KBP1):c.1948C>T(p.Arg650Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000155 in 1,097,447 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 8 hemizygotes in GnomAD. 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. R650Q) has been classified as Benign.
Frequency
Consequence
NM_031892.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SH3KBP1 | NM_031892.3 | c.1948C>T | p.Arg650Trp | missense_variant | 17/18 | ENST00000397821.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SH3KBP1 | ENST00000397821.8 | c.1948C>T | p.Arg650Trp | missense_variant | 17/18 | 1 | NM_031892.3 | P2 |
Frequencies
GnomAD3 genomes ? Cov.: 22
GnomAD4 exome AF: 0.0000155 AC: 17AN: 1097447Hom.: 0 Cov.: 29 AF XY: 0.0000221 AC XY: 8AN XY: 362805
GnomAD4 genome ? Cov.: 22
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 30, 2023 | This variant has not been reported in the literature in individuals affected with SH3KBP1-related conditions. This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 650 of the SH3KBP1 protein (p.Arg650Trp). This variant is not present in population databases (gnomAD no frequency). 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 SH3KBP1 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