12-111447026-G-C
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_005475.3(SH2B3):c.919G>C(p.Gly307Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000223 in 1,613,568 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_005475.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SH2B3 | ENST00000341259.7 | c.919G>C | p.Gly307Arg | missense_variant | Exon 4 of 8 | 1 | NM_005475.3 | ENSP00000345492.2 | ||
SH2B3 | ENST00000538307.1 | c.313G>C | p.Gly105Arg | missense_variant | Exon 3 of 7 | 2 | ENSP00000440597.1 | |||
ATXN2 | ENST00000642389.2 | n.*171-2839C>G | intron_variant | Intron 26 of 26 | ENSP00000496055.2 |
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152134Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000478 AC: 12AN: 250880Hom.: 0 AF XY: 0.0000369 AC XY: 5AN XY: 135628
GnomAD4 exome AF: 0.0000212 AC: 31AN: 1461434Hom.: 0 Cov.: 33 AF XY: 0.0000206 AC XY: 15AN XY: 727072
GnomAD4 genome AF: 0.0000329 AC: 5AN: 152134Hom.: 0 Cov.: 31 AF XY: 0.0000404 AC XY: 3AN XY: 74320
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
The p.G307R variant (also known as c.919G>C), located in coding exon 3 of the SH2B3 gene, results from a G to C substitution at nucleotide position 919. The glycine at codon 307 is replaced by arginine, an amino acid with dissimilar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at