12-111447360-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_005475.3(SH2B3):c.1052C>T(p.Ala351Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,760 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SH2B3 | NM_005475.3 | c.1052C>T | p.Ala351Val | missense_variant | 6/8 | ENST00000341259.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SH2B3 | ENST00000341259.7 | c.1052C>T | p.Ala351Val | missense_variant | 6/8 | 1 | NM_005475.3 | P1 | |
SH2B3 | ENST00000538307.1 | c.446C>T | p.Ala149Val | missense_variant | 5/7 | 2 | |||
ATXN2 | ENST00000642389.2 | c.*171-3173G>A | intron_variant, NMD_transcript_variant |
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251208Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135802
GnomAD4 exome AF: 0.00000479 AC: 7AN: 1461760Hom.: 0 Cov.: 34 AF XY: 0.00000825 AC XY: 6AN XY: 727190
GnomAD4 genome Cov.: 31
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 03, 2022 | The c.1052C>T (p.A351V) alteration is located in exon 6 (coding exon 5) of the SH2B3 gene. This alteration results from a C to T substitution at nucleotide position 1052, causing the alanine (A) at amino acid position 351 to be replaced by a valine (V). 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