9-127741791-G-T

Variant names:

• chr9-127741791-G-T
• NM_170600.3:c.2085C>A
• SH2D3C p.Ala695Ala

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_170600.3(SH2D3C):​c.2085C>A​(p.Ala695Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: SH2D3C NM_170600.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0970
• Publications: 0 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP7: Synonymous conserved (PhyloP=-0.097 with no splicing effect.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SH2D3C	NM_170600.3	MANE Select	c.2085C>A	p.Ala695Ala	synonymous	Exon 9 of 12	NP_733745.1	Q8N5H7-1
	SH2D3C	NM_001252334.2		c.1881C>A	p.Ala627Ala	synonymous	Exon 9 of 12	NP_001239263.1	Q8N5H7-4
	SH2D3C	NM_005489.4		c.1614C>A	p.Ala538Ala	synonymous	Exon 8 of 11	NP_005480.2	Q8N5H7-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SH2D3C	ENST00000314830.13	TSL:1 MANE Select	c.2085C>A	p.Ala695Ala	synonymous	Exon 9 of 12	ENSP00000317817.8	Q8N5H7-1
	SH2D3C	ENST00000373276.7	TSL:1	c.1881C>A	p.Ala627Ala	synonymous	Exon 9 of 12	ENSP00000362373.3	Q8N5H7-4
	SH2D3C	ENST00000373277.8	TSL:1	c.1614C>A	p.Ala538Ala	synonymous	Exon 8 of 11	ENSP00000362374.4	Q8N5H7-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 60

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	8.0
DANN	Benign	0.79
PhyloP100		-0.097

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr9-130504070;