rs749171361
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_001122681.2(SH3BP2):āc.1187T>Cā(p.Met396Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000162 in 1,608,122 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/20 in silico tools predict a benign 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. M396V) has been classified as Uncertain significance.
Frequency
Consequence
NM_001122681.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SH3BP2 | NM_001122681.2 | c.1187T>C | p.Met396Thr | missense_variant | 8/13 | ENST00000503393.8 | |
SH3BP2 | NM_001145856.2 | c.1358T>C | p.Met453Thr | missense_variant | 8/13 | ||
SH3BP2 | NM_001145855.2 | c.1271T>C | p.Met424Thr | missense_variant | 8/13 | ||
SH3BP2 | NM_003023.4 | c.1187T>C | p.Met396Thr | missense_variant | 8/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SH3BP2 | ENST00000503393.8 | c.1187T>C | p.Met396Thr | missense_variant | 8/13 | 1 | NM_001122681.2 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152252Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000334 AC: 8AN: 239636Hom.: 0 AF XY: 0.0000228 AC XY: 3AN XY: 131392
GnomAD4 exome AF: 0.0000158 AC: 23AN: 1455870Hom.: 0 Cov.: 36 AF XY: 0.0000138 AC XY: 10AN XY: 724298
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152252Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74386
ClinVar
Submissions by phenotype
Fibrous dysplasia of jaw Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 11, 2023 | 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: 454490). This variant has not been reported in the literature in individuals affected with SH3BP2-related conditions. This variant is present in population databases (rs749171361, gnomAD 0.01%). This sequence change replaces methionine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 396 of the SH3BP2 protein (p.Met396Thr). 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