Variant 9-127744627-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_170600.3(SH2D3C):c.1737G>A(p.Lys579=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00804 in 1,614,034 control chromosomes in the GnomAD database, including 127 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0062 ( 8 hom., cov: 30)

Exomes 𝑓: 0.0082 ( 119 hom. )

Consequence

SH2D3C
NM_170600.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.767

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.39).

BP6

Variant 9-127744627-C-T is Benign according to our data. Variant chr9-127744627-C-T is described in ClinVar as [Benign]. Clinvar id is 775279.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.767 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00619 (943/152314) while in subpopulation SAS AF= 0.0226 (109/4828). AF 95% confidence interval is 0.0191. There are 8 homozygotes in gnomad4. There are 453 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 8 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SH2D3C	NM_170600.3 linkuse as main transcript	c.1737G>A	p.Lys579=	synonymous_variant	7/12	ENST00000314830.13	NP_733745.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SH2D3C	ENST00000314830.13 linkuse as main transcript	c.1737G>A	p.Lys579=	synonymous_variant	7/12	1	NM_170600.3	ENSP00000317817	P3	Q8N5H7-1

Frequencies

GnomAD3 genomes

AF:

0.00618

AC:

940

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00544

Gnomad ASJ

AF:

0.0374

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0221

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00788

Gnomad OTH

AF:

0.00908

GnomAD3 exomes

AF:

0.00870

AC:

2187

AN:

251404

Hom.:

AF XY:

0.00976

AC XY:

1326

AN XY:

135878

show subpopulations

Gnomad AFR exome

AF:

0.00123

Gnomad AMR exome

AF:

0.00393

Gnomad ASJ exome

AF:

0.0390

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.0231

Gnomad FIN exome

AF:

0.000139

Gnomad NFE exome

AF:

0.00755

Gnomad OTH exome

AF:

0.0111

GnomAD4 exome

AF:

0.00824

AC:

12040

AN:

1461720

Hom.:

119

Cov.:

AF XY:

0.00889

AC XY:

6462

AN XY:

727122

show subpopulations

Gnomad4 AFR exome

AF:

0.00140

Gnomad4 AMR exome

AF:

0.00391

Gnomad4 ASJ exome

AF:

0.0409

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.0232

Gnomad4 FIN exome

AF:

0.000300

Gnomad4 NFE exome

AF:

0.00710

Gnomad4 OTH exome

AF:

0.0101

GnomAD4 genome

AF:

0.00619

AC:

943

AN:

152314

Hom.:

Cov.:

AF XY:

0.00608

AC XY:

453

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.00144

Gnomad4 AMR

AF:

0.00543

Gnomad4 ASJ

AF:

0.0374

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0226

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.00788

Gnomad4 OTH

AF:

0.00946

Alfa

AF:

0.00939

Hom.:

Bravo

AF:

0.00609

Asia WGS

AF:

0.00837

AC:

AN:

3478

EpiCase

AF:

0.00927

EpiControl

AF:

0.0104

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 23, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Benign

0.57

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