NM_053282.5:c.355A>G

Variant names:

• chr1-162398931-T-C
• rs903322546
• NM_053282.5:c.355A>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_053282.5(SH2D1B):​c.355A>G​(p.Thr119Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SH2D1B NM_053282.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.08

Genes affected

SH2D1B (HGNC:30416): (SH2 domain containing 1B) By binding phosphotyrosines through its free SRC (MIM 190090) homology-2 (SH2) domain, EAT2 regulates signal transduction through receptors expressed on the surface of antigen-presenting cells (Morra et al., 2001 [PubMed 11689425]).[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04816693).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SH2D1B	NM_053282.5	c.355A>G	p.Thr119Ala	missense_variant	Exon 3 of 4	ENST00000367929.3	NP_444512.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SH2D1B	ENST00000367929.3	c.355A>G	p.Thr119Ala	missense_variant	Exon 3 of 4	1	NM_053282.5	ENSP00000356906.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 07, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.355A>G (p.T119A) alteration is located in exon 3 (coding exon 3) of the SH2D1B gene. This alteration results from a A to G substitution at nucleotide position 355, causing the threonine (T) at amino acid position 119 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	0.12
DANN	Benign	0.25
DEOGEN2	Benign	0.068	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.0028	N
LIST_S2	Benign	0.22	T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.048	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.36	N
REVEL	Benign	0.087
Sift	Benign	0.80	T
Sift4G	Benign	0.34	T
Polyphen		0.042	B
Vest4		0.045
MutPred		0.25		Gain of sheet (P = 0.1208);
MVP		0.56
MPC		0.090
ClinPred		0.069	T
GERP RS		-8.9
Varity_R		0.023
gMVP		0.14

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs903322546; hg19: chr1-162368721;