9-127744816-C-G

Variant names:

• chr9-127744816-C-G
• rs1938826541
• NM_170600.3:c.1548G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_170600.3(SH2D3C):​c.1548G>C​(p.Gln516His) variant causes a missense 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. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: SH2D3C NM_170600.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.410
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0778341).

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.1548G>C	p.Gln516His	missense	Exon 7 of 12	NP_733745.1	Q8N5H7-1
	SH2D3C	NM_001252334.2		c.1344G>C	p.Gln448His	missense	Exon 7 of 12	NP_001239263.1	Q8N5H7-4
	SH2D3C	NM_005489.4		c.1077G>C	p.Gln359His	missense	Exon 6 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.1548G>C	p.Gln516His	missense	Exon 7 of 12	ENSP00000317817.8	Q8N5H7-1
	SH2D3C	ENST00000373276.7	TSL:1	c.1344G>C	p.Gln448His	missense	Exon 7 of 12	ENSP00000362373.3	Q8N5H7-4
	SH2D3C	ENST00000373277.8	TSL:1	c.1077G>C	p.Gln359His	missense	Exon 6 of 11	ENSP00000362374.4	Q8N5H7-2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	9.7
DANN	Benign	0.97
DEOGEN2	Benign	0.053	T
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.55
FATHMM_MKL	Benign	0.30	N
LIST_S2	Benign	0.47	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.078	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PhyloP100		-0.41
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.48	N
REVEL	Benign	0.020
Sift	Benign	0.13	T
Sift4G	Benign	0.35	T
Polyphen		0.084	B
Vest4		0.15
MutPred		0.15		Loss of MoRF binding (P = 0.102)
MVP		0.51
MPC		0.37
ClinPred		0.10	T
GERP RS		1.4
Varity_R		0.060
gMVP		0.22
Mutation Taster		=92/8	polymorphism

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: rs1938826541; hg19: chr9-130507095;