chr12-111418689-T-C
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_005475.3(SH2B3):c.544T>C(p.Phe182Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.019 in 1,489,174 control chromosomes in the GnomAD database, including 4,489 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.
Frequency
Consequence
NM_005475.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SH2B3 | NM_005475.3 | c.544T>C | p.Phe182Leu | missense_variant | 2/8 | ENST00000341259.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SH2B3 | ENST00000341259.7 | c.544T>C | p.Phe182Leu | missense_variant | 2/8 | 1 | NM_005475.3 | P1 | |
SH2B3 | ENST00000550925.2 | c.352T>C | p.Phe118Leu | missense_variant | 1/2 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.102 AC: 15497AN: 151744Hom.: 2648 Cov.: 32
GnomAD3 exomes AF: 0.00936 AC: 894AN: 95508Hom.: 78 AF XY: 0.00795 AC XY: 435AN XY: 54734
GnomAD4 exome AF: 0.00954 AC: 12760AN: 1337322Hom.: 1822 Cov.: 32 AF XY: 0.00855 AC XY: 5649AN XY: 661004
GnomAD4 genome ? AF: 0.102 AC: 15561AN: 151852Hom.: 2667 Cov.: 32 AF XY: 0.0985 AC XY: 7310AN XY: 74246
ClinVar
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | May 09, 2023 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 10, 2019 | - - |
SH2B3-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Nov 07, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at