12-111447506-G-A
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4BS1_SupportingBS2
The NM_005475.3(SH2B3):c.1198G>A(p.Glu400Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00144 in 1,488,994 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts 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 Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SH2B3 | ENST00000341259.7 | c.1198G>A | p.Glu400Lys | missense_variant | Exon 6 of 8 | 1 | NM_005475.3 | ENSP00000345492.2 | ||
SH2B3 | ENST00000538307.1 | c.592G>A | p.Glu198Lys | missense_variant | Exon 5 of 7 | 2 | ENSP00000440597.1 | |||
ATXN2 | ENST00000642389.2 | n.*171-3319C>T | intron_variant | Intron 26 of 26 | ENSP00000496055.2 |
Frequencies
GnomAD3 genomes AF: 0.000791 AC: 108AN: 136538Hom.: 0 Cov.: 30
GnomAD3 exomes AF: 0.000582 AC: 144AN: 247234Hom.: 0 AF XY: 0.000581 AC XY: 78AN XY: 134160
GnomAD4 exome AF: 0.00151 AC: 2042AN: 1352362Hom.: 3 Cov.: 34 AF XY: 0.00148 AC XY: 991AN XY: 669924
GnomAD4 genome AF: 0.000790 AC: 108AN: 136632Hom.: 0 Cov.: 30 AF XY: 0.000731 AC XY: 47AN XY: 64306
ClinVar
Submissions by phenotype
not provided Uncertain:3
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Observed heterozygous in individuals with myelodysplastic syndrome/myeloproliferative neoplasm, juvenile myelomonocytic leukemia, or idiopathic erythrocytosis (PMID: 21990094, 26457647, 27651169, 31173385); Published functional studies demonstrate normal cell growth inhibition (PMID: 21990094); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 26607381, 24777453, 27651169, 28484264, 24725463, 31173385, 26457647, 29682367, 33792220, Butler2022[FunctionalStudy], 34662886, 35281324, 35056081, 36324816, 35935937, 38262687, 38417019, 21990094, 33850299, 38862854) -
PM1 -
Primary myelofibrosis;C3277671:Thrombocythemia 1;C4551637:Primary familial polycythemia due to EPO receptor mutation Uncertain:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at