chr16-28866221-C-T
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_001387430.1(SH2B1):c.127C>T(p.Arg43Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000242 in 1,609,326 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 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. R43S) has been classified as Uncertain significance.
Frequency
Consequence
NM_001387430.1 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SH2B1 | NM_001387430.1 | c.127C>T | p.Arg43Cys | missense_variant | 1/8 | ENST00000684370.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SH2B1 | ENST00000684370.1 | c.127C>T | p.Arg43Cys | missense_variant | 1/8 | NM_001387430.1 | P3 |
Frequencies
GnomAD3 genomes AF: 0.0000724 AC: 11AN: 152038Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000211 AC: 5AN: 236518Hom.: 0 AF XY: 0.00000769 AC XY: 1AN XY: 130064
GnomAD4 exome AF: 0.0000192 AC: 28AN: 1457172Hom.: 0 Cov.: 35 AF XY: 0.0000221 AC XY: 16AN XY: 724796
GnomAD4 genome AF: 0.0000723 AC: 11AN: 152154Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74360
ClinVar
Submissions by phenotype
SH2B1-related disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Feb 06, 2024 | The SH2B1 c.127C>T variant is predicted to result in the amino acid substitution p.Arg43Cys. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.022% of alleles in individuals of African descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at