rs369562627
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PP3_Moderate
The NM_001122681.2(SH3BP2):c.1534C>T(p.Arg512Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000217 in 1,614,076 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 (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R512H) has been classified as Uncertain significance.
Frequency
Consequence
NM_001122681.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SH3BP2 | NM_001122681.2 | c.1534C>T | p.Arg512Cys | missense_variant | 12/13 | ENST00000503393.8 | |
SH3BP2 | NM_001145856.2 | c.1705C>T | p.Arg569Cys | missense_variant | 12/13 | ||
SH3BP2 | NM_001145855.2 | c.1618C>T | p.Arg540Cys | missense_variant | 12/13 | ||
SH3BP2 | NM_003023.4 | c.1534C>T | p.Arg512Cys | missense_variant | 12/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SH3BP2 | ENST00000503393.8 | c.1534C>T | p.Arg512Cys | missense_variant | 12/13 | 1 | NM_001122681.2 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152216Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251398Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135904
GnomAD4 exome AF: 0.0000219 AC: 32AN: 1461860Hom.: 0 Cov.: 31 AF XY: 0.0000289 AC XY: 21AN XY: 727234
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152216Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74378
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 20, 2023 | The c.1534C>T (p.R512C) alteration is located in exon 12 (coding exon 11) of the SH3BP2 gene. This alteration results from a C to T substitution at nucleotide position 1534, causing the arginine (R) at amino acid position 512 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Fibrous dysplasia of jaw Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Apr 24, 2023 | 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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 SH3BP2 protein function. ClinVar contains an entry for this variant (Variation ID: 577475). This variant has not been reported in the literature in individuals affected with SH3BP2-related conditions. This variant is present in population databases (rs369562627, gnomAD 0.005%). This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 512 of the SH3BP2 protein (p.Arg512Cys). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at