rs514024

Variant names:

• chr9-127741791-G-A
• rs514024
• NM_170600.3:c.2085C>T

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_170600.3(SH2D3C):​c.2085C>T​(p.Ala695Ala) 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
• Publications: 30 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_170600.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SH2D3C	NM_170600.3	MANE Select	c.2085C>T	p.Ala695Ala	synonymous	Exon 9 of 12	NP_733745.1
	SH2D3C	NM_001252334.2		c.1881C>T	p.Ala627Ala	synonymous	Exon 9 of 12	NP_001239263.1
	SH2D3C	NM_005489.4		c.1614C>T	p.Ala538Ala	synonymous	Exon 8 of 11	NP_005480.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SH2D3C	ENST00000314830.13	TSL:1 MANE Select	c.2085C>T	p.Ala695Ala	synonymous	Exon 9 of 12	ENSP00000317817.8
	SH2D3C	ENST00000373276.7	TSL:1	c.1881C>T	p.Ala627Ala	synonymous	Exon 9 of 12	ENSP00000362373.3
	SH2D3C	ENST00000373277.8	TSL:1	c.1614C>T	p.Ala538Ala	synonymous	Exon 8 of 11	ENSP00000362374.4

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

GnomAD2 exomes AF: 0.563 AC: 138924 AN: 246932 AF XY: 0.568

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 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

African (AFR) AF: 0.565 AC: 18932 AN: 33480

American (AMR) AF: 0.550 AC: 24572 AN: 44684

Ashkenazi Jewish (ASJ) AF: 0.601 AC: 15701 AN: 26112

East Asian (EAS) AF: 0.294 AC: 11682 AN: 39692

South Asian (SAS) AF: 0.628 AC: 54097 AN: 86200

European-Finnish (FIN) AF: 0.646 AC: 33829 AN: 52406

Middle Eastern (MID) AF: 0.633 AC: 3647 AN: 5762

European-Non Finnish (NFE) AF: 0.568 AC: 631546 AN: 1111728

Other (OTH) AF: 0.567 AC: 34252 AN: 60366

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

African (AFR) AF: 0.568 AC: 23540 AN: 41478

American (AMR) AF: 0.568 AC: 8676 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.589 AC: 2045 AN: 3472

East Asian (EAS) AF: 0.288 AC: 1489 AN: 5174

South Asian (SAS) AF: 0.633 AC: 3058 AN: 4828

European-Finnish (FIN) AF: 0.655 AC: 6920 AN: 10570

Middle Eastern (MID) AF: 0.612 AC: 180 AN: 294

European-Non Finnish (NFE) AF: 0.575 AC: 39102 AN: 67968

Other (OTH) AF: 0.575 AC: 1215 AN: 2112

Alfa AF: 0.569 Hom.: 97527

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	8.9
DANN	Benign	0.84
PhyloP100		-0.097
Mutation Taster		=96/4	polymorphism (auto)

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

Other links and lift over

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