Variant 9-127741826-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_170600.3(SH2D3C):c.2050A>G(p.Ser684Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,461,046 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict 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: 33)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

SH2D3C
NM_170600.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.39

Variant links:

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]

SH2D3C links:

SH2D3C (HGNC:):

SH2D3C links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.17159763).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SH2D3C	NM_170600.3 linkuse as main transcript	c.2050A>G	p.Ser684Gly	missense_variant	9/12	ENST00000314830.13	NP_733745.1	Q8N5H7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SH2D3C	ENST00000314830.13 linkuse as main transcript	c.2050A>G	p.Ser684Gly	missense_variant	9/12	1	NM_170600.3	ENSP00000317817.8		Q8N5H7-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000401

AC:

AN:

249678

Hom.:

AF XY:

0.00000739

AC XY:

AN XY:

135390

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000891

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461046

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726842

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000360

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 22, 2024

The c.2050A>G (p.S684G) alteration is located in exon 9 (coding exon 9) of the SH2D3C gene. This alteration results from a A to G substitution at nucleotide position 2050, causing the serine (S) at amino acid position 684 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.088

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.081

.;.;.;.;T;.

Eigen

Benign

-0.38

Eigen_PC

Benign

-0.15

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.91

D;D;D;D;D;D

M_CAP

Benign

0.011

MetaRNN

Benign

0.17

T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.58

.;.;.;.;N;.

PrimateAI

Uncertain

0.69

PROVEAN

Benign

0.22

N;N;N;N;N;.

REVEL

Benign

0.21

Sift

Benign

0.40

T;T;T;T;T;.

Sift4G

Benign

0.75

T;T;T;T;T;T

Polyphen

0.030

B;B;.;.;B;.

Vest4

0.30

MutPred

0.43

.;.;.;.;Gain of helix (P = 0.132);.;

MVP

0.66

MPC

0.65

ClinPred

0.18

GERP RS

5.9

Varity_R

0.43

gMVP

0.58

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over