12-111446775-C-G
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_005475.3(SH2B3):c.755C>G(p.Ala252Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000572 in 1,399,120 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SH2B3 | NM_005475.3 | c.755C>G | p.Ala252Gly | missense_variant | 3/8 | ENST00000341259.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SH2B3 | ENST00000341259.7 | c.755C>G | p.Ala252Gly | missense_variant | 3/8 | 1 | NM_005475.3 | P1 | |
SH2B3 | ENST00000538307.1 | c.149C>G | p.Ala50Gly | missense_variant | 2/7 | 2 | |||
ATXN2 | ENST00000642389.2 | c.*171-2588G>C | intron_variant, NMD_transcript_variant |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.0000244 AC: 5AN: 204652Hom.: 0 AF XY: 0.0000278 AC XY: 3AN XY: 108004
GnomAD4 exome AF: 0.00000572 AC: 8AN: 1399120Hom.: 0 Cov.: 29 AF XY: 0.00000872 AC XY: 6AN XY: 688248
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 14, 2023 | The c.755C>G (p.A252G) alteration is located in exon 3 (coding exon 2) of the SH2B3 gene. This alteration results from a C to G substitution at nucleotide position 755, causing the alanine (A) at amino acid position 252 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at