19-6760963-T-G

Position:

• chr19-6760963-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005490.3(SH2D3A):​c.94A>C​(p.Asn32His) 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. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N32D) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SH2D3A NM_005490.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.379

Genes affected

SH2D3A (HGNC:16885): (SH2 domain containing 3A) Predicted to enable guanyl-nucleotide exchange factor activity and phosphotyrosine residue binding activity. Predicted to be involved in positive regulation of peptidyl-serine phosphorylation. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23883373).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SH2D3A	NM_005490.3	c.94A>C	p.Asn32His	missense_variant	3/10	ENST00000245908.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SH2D3A	ENST00000245908.11	c.94A>C	p.Asn32His	missense_variant	3/10	1	NM_005490.3	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.22	T;.
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.44
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.69	T;T
M_CAP	Benign	0.034	D
MetaRNN	Benign	0.24	T;T
MetaSVM	Benign	-0.86	T
MutationAssessor	Benign	0.27	N;.
MutationTaster	Benign	1.0	P;P
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-1.8	N;.
REVEL	Benign	0.064
Sift	Benign	0.068	T;.
Sift4G	Uncertain	0.021	D;D
Polyphen		0.017	B;.
Vest4		0.25
MutPred		0.36		Gain of disorder (P = 0.1194);Gain of disorder (P = 0.1194);
MVP		0.56
MPC		0.28
ClinPred		0.63	D
GERP RS		3.7
Varity_R		0.074
gMVP		0.40

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs7258236; hg19: chr19-6760974;