9-127770709-A-C

Position:

• chr9-127770709-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_170600.3(SH2D3C):​c.515+3281T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.646 in 152,122 control chromosomes in the GnomAD database, including 32,550 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 0.65 (32550 hom., cov: 33)
• Consequence: SH2D3C NM_170600.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0560

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.945 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SH2D3C	NM_170600.3	c.515+3281T>G		intron_variant		ENST00000314830.13	NP_733745.1
SH2D3C	NM_001252334.2	c.-61+477T>G		intron_variant			NP_001239263.1
SH2D3C	NM_005489.4	c.44+477T>G		intron_variant			NP_005480.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SH2D3C	ENST00000314830.13	c.515+3281T>G		intron_variant		1	NM_170600.3	ENSP00000317817	P3

Frequencies

GnomAD3 genomes AF: 0.646 AC: 98210 AN: 152004 Hom.: 32520 Cov.: 33

Gnomad AFR AF: 0.757

Gnomad AMI AF: 0.685

Gnomad AMR AF: 0.609

Gnomad ASJ AF: 0.526

Gnomad EAS AF: 0.967

Gnomad SAS AF: 0.696

Gnomad FIN AF: 0.532

Gnomad MID AF: 0.601

Gnomad NFE AF: 0.583

Gnomad OTH AF: 0.633

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.646 AC: 98287 AN: 152122 Hom.: 32550 Cov.: 33 AF XY: 0.645 AC XY: 47987 AN XY: 74366

Gnomad4 AFR AF: 0.757

Gnomad4 AMR AF: 0.608

Gnomad4 ASJ AF: 0.526

Gnomad4 EAS AF: 0.968

Gnomad4 SAS AF: 0.694

Gnomad4 FIN AF: 0.532

Gnomad4 NFE AF: 0.583

Gnomad4 OTH AF: 0.630

Alfa AF: 0.578 Hom.: 10229

Bravo AF: 0.657

Asia WGS AF: 0.805 AC: 2802 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.5
DANN	Benign	0.71

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: rs913989; hg19: chr9-130532988;