rs514024

Positions:

• chr9-127741791-G-A
• chr9-127741791-G-C

Variant summary

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

The NM_170600.3(SH2D3C):​c.2085C>T​(p.Ala695=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.567 in 1,612,512 control chromosomes in the GnomAD database, including 262,328 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 0.57 (25030 hom., cov: 32)
  • Exomes 𝑓: 0.57 (237298 hom.)
• Consequence: SH2D3C NM_170600.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0970

Genes affected

SH2D3C (HGNC:16884): (SH2 domain containing 3C) This gene encodes an adaptor protein and member of a cytoplasmic protein family involved in cell migration. The encoded protein contains a putative Src homology 2 (SH2) domain and guanine nucleotide exchange factor-like domain which allows this signaling protein to form a complex with scaffolding protein Crk-associated substrate. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2011]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BP7: Synonymous conserved (PhyloP=-0.097 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.615 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SH2D3C	NM_170600.3	c.2085C>T	p.Ala695=	synonymous_variant	9/12	ENST00000314830.13	NP_733745.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SH2D3C	ENST00000314830.13	c.2085C>T	p.Ala695=	synonymous_variant	9/12	1	NM_170600.3	ENSP00000317817	P3

Frequencies

GnomAD3 genomes AF: 0.570 AC: 86579 AN: 151964 Hom.: 25002 Cov.: 32

Gnomad AFR AF: 0.568

Gnomad AMI AF: 0.462

Gnomad AMR AF: 0.567

Gnomad ASJ AF: 0.589

Gnomad EAS AF: 0.288

Gnomad SAS AF: 0.633

Gnomad FIN AF: 0.655

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.575

Gnomad OTH AF: 0.576

GnomAD3 exomes AF: 0.563 AC: 138924 AN: 246932 Hom.: 40113 AF XY: 0.568 AC XY: 76257 AN XY: 134242

Gnomad AFR exome AF: 0.566

Gnomad AMR exome AF: 0.547

Gnomad ASJ exome AF: 0.599

Gnomad EAS exome AF: 0.271

Gnomad SAS exome AF: 0.628

Gnomad FIN exome AF: 0.647

Gnomad NFE exome AF: 0.577

Gnomad OTH exome AF: 0.573

GnomAD4 exome AF: 0.567 AC: 828258 AN: 1460430 Hom.: 237298 Cov.: 60 AF XY: 0.570 AC XY: 413793 AN XY: 726528

Gnomad4 AFR exome AF: 0.565

Gnomad4 AMR exome AF: 0.550

Gnomad4 ASJ exome AF: 0.601

Gnomad4 EAS exome AF: 0.294

Gnomad4 SAS exome AF: 0.628

Gnomad4 FIN exome AF: 0.646

Gnomad4 NFE exome AF: 0.568

Gnomad4 OTH exome AF: 0.567

GnomAD4 genome AF: 0.570 AC: 86645 AN: 152082 Hom.: 25030 Cov.: 32 AF XY: 0.573 AC XY: 42599 AN XY: 74344

Gnomad4 AFR AF: 0.568

Gnomad4 AMR AF: 0.568

Gnomad4 ASJ AF: 0.589

Gnomad4 EAS AF: 0.288

Gnomad4 SAS AF: 0.633

Gnomad4 FIN AF: 0.655

Gnomad4 NFE AF: 0.575

Gnomad4 OTH AF: 0.575

Alfa AF: 0.571 Hom.: 43517

Bravo AF: 0.559

Asia WGS AF: 0.501 AC: 1742 AN: 3478

EpiCase AF: 0.580

EpiControl AF: 0.580

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	8.9
DANN	Benign	0.84

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: rs514024; hg19: chr9-130504070; COSMIC: COSV59122113; COSMIC: COSV59122113;