rs1969385379

Variant names:

• chr19-6752702-C-A
• NM_005490.3:c.1622G>T

Your query was ambiguous. Multiple possible variants found:

• chr19-6752702-C-A
• chr19-6752702-C-G
• chr19-6752702-C-T

Variant summary

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

The NM_005490.3(SH2D3A):​c.1622G>T​(p.Arg541Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000714 in 1,399,960 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: SH2D3A NM_005490.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.27

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=0.13912192).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SH2D3A	NM_005490.3	c.1622G>T	p.Arg541Leu	missense_variant	Exon 10 of 10	ENST00000245908.11	NP_005481.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SH2D3A	ENST00000245908.11	c.1622G>T	p.Arg541Leu	missense_variant	Exon 10 of 10	1	NM_005490.3	ENSP00000245908.5
SH2D3A	ENST00000437152.7	c.1343G>T	p.Arg448Leu	missense_variant	Exon 8 of 8	2		ENSP00000393303.2
SH2D3A	ENST00000597168.1	n.444-474G>T		intron_variant	Intron 2 of 2	5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.14e-7 AC: 1 AN: 1399960 Hom.: 0 Cov.: 31 AF XY: 0.00000145 AC XY: 1 AN XY: 690598

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.26e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	8.1
DANN	Benign	0.85
DEOGEN2	Benign	0.0047	.;T
Eigen	Benign	-0.98
Eigen_PC	Benign	-0.97
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.69	T;T
M_CAP	Benign	0.0064	T
MetaRNN	Benign	0.14	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.41	.;N
PrimateAI	Benign	0.36	T
PROVEAN	Benign	1.9	N;N
REVEL	Benign	0.085
Sift	Benign	0.47	T;T
Sift4G	Benign	0.35	T;T
Polyphen		0.0	.;B
Vest4		0.12
MutPred		0.44		.;Loss of MoRF binding (P = 0.0186);
MVP		0.45
MPC		1.6
ClinPred		0.043	T
GERP RS		-3.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.046
gMVP		0.35

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-6752713;