chr4-2822965-G-A
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_001122681.2(SH3BP2):c.167G>A(p.Arg56His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000372 in 1,614,054 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R56C) has been classified as Likely benign.
Frequency
Consequence
NM_001122681.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SH3BP2 | NM_001122681.2 | c.167G>A | p.Arg56His | missense_variant | 3/13 | ENST00000503393.8 | |
SH3BP2 | NM_001145856.2 | c.338G>A | p.Arg113His | missense_variant | 3/13 | ||
SH3BP2 | NM_001145855.2 | c.251G>A | p.Arg84His | missense_variant | 3/13 | ||
SH3BP2 | NM_003023.4 | c.167G>A | p.Arg56His | missense_variant | 3/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SH3BP2 | ENST00000503393.8 | c.167G>A | p.Arg56His | missense_variant | 3/13 | 1 | NM_001122681.2 | P2 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251282Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135814
GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461774Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2AN XY: 727174
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152280Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74460
ClinVar
Submissions by phenotype
Fibrous dysplasia of jaw Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Apr 15, 2018 | Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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. This variant has not been reported in the literature in individuals with SH3BP2-related disease. This variant is present in population databases (rs779608979, ExAC 0.009%). This sequence change replaces arginine with histidine at codon 56 of the SH3BP2 protein (p.Arg56His). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and histidine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at