rs2305806

Positions:

• chr19-6754996-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_005490.3(SH2D3A):​c.816A>G​(p.Thr272=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.292 in 1,613,586 control chromosomes in the GnomAD database, including 71,201 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.34 (9470 hom., cov: 30)
  • Exomes 𝑓: 0.29 (61731 hom.)
• Consequence: SH2D3A NM_005490.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.145

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 Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP7: Synonymous conserved (PhyloP=0.145 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.453 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SH2D3A	NM_005490.3	c.816A>G	p.Thr272=	synonymous_variant	5/10	ENST00000245908.11	NP_005481.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SH2D3A	ENST00000245908.11	c.816A>G	p.Thr272=	synonymous_variant	5/10	1	NM_005490.3	ENSP00000245908	P1

Frequencies

GnomAD3 genomes AF: 0.341 AC: 51745 AN: 151736 Hom.: 9451 Cov.: 30

Gnomad AFR AF: 0.458

Gnomad AMI AF: 0.293

Gnomad AMR AF: 0.303

Gnomad ASJ AF: 0.224

Gnomad EAS AF: 0.326

Gnomad SAS AF: 0.200

Gnomad FIN AF: 0.377

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.292

Gnomad OTH AF: 0.319

GnomAD3 exomes AF: 0.299 AC: 75022 AN: 250580 Hom.: 11903 AF XY: 0.291 AC XY: 39395 AN XY: 135606

Gnomad AFR exome AF: 0.465

Gnomad AMR exome AF: 0.294

Gnomad ASJ exome AF: 0.233

Gnomad EAS exome AF: 0.324

Gnomad SAS exome AF: 0.199

Gnomad FIN exome AF: 0.364

Gnomad NFE exome AF: 0.295

Gnomad OTH exome AF: 0.296

GnomAD4 exome AF: 0.287 AC: 419921 AN: 1461732 Hom.: 61731 Cov.: 50 AF XY: 0.284 AC XY: 206307 AN XY: 727154

Gnomad4 AFR exome AF: 0.461

Gnomad4 AMR exome AF: 0.295

Gnomad4 ASJ exome AF: 0.234

Gnomad4 EAS exome AF: 0.300

Gnomad4 SAS exome AF: 0.203

Gnomad4 FIN exome AF: 0.362

Gnomad4 NFE exome AF: 0.285

Gnomad4 OTH exome AF: 0.292

GnomAD4 genome AF: 0.341 AC: 51816 AN: 151854 Hom.: 9470 Cov.: 30 AF XY: 0.342 AC XY: 25384 AN XY: 74206

Gnomad4 AFR AF: 0.458

Gnomad4 AMR AF: 0.303

Gnomad4 ASJ AF: 0.224

Gnomad4 EAS AF: 0.326

Gnomad4 SAS AF: 0.201

Gnomad4 FIN AF: 0.377

Gnomad4 NFE AF: 0.292

Gnomad4 OTH AF: 0.322

Alfa AF: 0.291 Hom.: 15190

Bravo AF: 0.343

Asia WGS AF: 0.277 AC: 965 AN: 3478

EpiCase AF: 0.274

EpiControl AF: 0.283

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.1
DANN	Benign	0.51

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

LitVar

Other links and lift over

dbSNP: rs2305806; hg19: chr19-6755007; COSMIC: COSV55584576; COSMIC: COSV55584576;