Variant 7-80749003-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_006379.5(SEMA3C):c.1737C>G(p.Val579Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.97 in 1,611,996 control chromosomes in the GnomAD database, including 761,424 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.91 ( 64175 hom., cov: 31)

Exomes 𝑓: 0.98 ( 697249 hom. )

Consequence

SEMA3C
NM_006379.5 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.413

Variant links:

Genes affected

SEMA3C (HGNC:10725): (semaphorin 3C) This gene encodes a secreted glycoprotein that belongs to the semaphorin class 3 family of neuronal guidance cues. The encoded protein contains an N-terminal sema domain, integrin and immunoglobulin-like domains, and a C-terminal basic domain. Homodimerization and proteolytic cleavage of the C-terminal propeptide are necessary for the function of the encoded protein. It binds a neuropilin co-receptor before forming a heterotrimeric complex with an associated plexin. An increase in the expression of this gene correlates with an increase in cancer cell invasion and adhesion. Naturally occurring mutations in this gene are associated with Hirschsprung disease. [provided by RefSeq, May 2017]

SEMA3C links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BP6

Variant 7-80749003-G-C is Benign according to our data. Variant chr7-80749003-G-C is described in ClinVar as [Benign]. Clinvar id is 3060860.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=0.413 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.987 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEMA3C	NM_006379.5 linkuse as main transcript	c.1737C>G	p.Val579Val	synonymous_variant	17/18	ENST00000265361.8	NP_006370.1	Q99985-1
SEMA3C	NM_001350120.2 linkuse as main transcript	c.1791C>G	p.Val597Val	synonymous_variant	17/18		NP_001337049.1
SEMA3C	NM_001350121.2 linkuse as main transcript	c.1563C>G	p.Val521Val	synonymous_variant	18/19		NP_001337050.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEMA3C	ENST00000265361.8 linkuse as main transcript	c.1737C>G	p.Val579Val	synonymous_variant	17/18	1	NM_006379.5	ENSP00000265361.3		Q99985-1
SEMA3C	ENST00000419255.6 linkuse as main transcript	c.1737C>G	p.Val579Val	synonymous_variant	17/18	2		ENSP00000411193.2		Q99985-1

Frequencies

GnomAD3 genomes

AF:

0.913

AC:

138705

AN:

152004

Hom.:

64165

Cov.:

show subpopulations

Gnomad AFR

AF:

0.760

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.936

Gnomad ASJ

AF:

0.975

Gnomad EAS

AF:

0.763

Gnomad SAS

AF:

0.939

Gnomad FIN

AF:

0.983

Gnomad MID

AF:

0.968

Gnomad NFE

AF:

0.993

Gnomad OTH

AF:

0.938

GnomAD3 exomes

AF:

0.942

AC:

234834

AN:

249162

Hom.:

111450

AF XY:

0.949

AC XY:

127740

AN XY:

134616

show subpopulations

Gnomad AFR exome

AF:

0.760

Gnomad AMR exome

AF:

0.912

Gnomad ASJ exome

AF:

0.978

Gnomad EAS exome

AF:

0.764

Gnomad SAS exome

AF:

0.953

Gnomad FIN exome

AF:

0.983

Gnomad NFE exome

AF:

0.992

Gnomad OTH exome

AF:

0.962

GnomAD4 exome

AF:

0.976

AC:

1424727

AN:

1459874

Hom.:

697249

Cov.:

AF XY:

0.976

AC XY:

708842

AN XY:

726230

show subpopulations

Gnomad4 AFR exome

AF:

0.752

Gnomad4 AMR exome

AF:

0.913

Gnomad4 ASJ exome

AF:

0.977

Gnomad4 EAS exome

AF:

0.799

Gnomad4 SAS exome

AF:

0.953

Gnomad4 FIN exome

AF:

0.984

Gnomad4 NFE exome

AF:

0.994

Gnomad4 OTH exome

AF:

0.955

GnomAD4 genome

AF:

0.912

AC:

138766

AN:

152122

Hom.:

64175

Cov.:

AF XY:

0.912

AC XY:

67840

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.759

Gnomad4 AMR

AF:

0.935

Gnomad4 ASJ

AF:

0.975

Gnomad4 EAS

AF:

0.762

Gnomad4 SAS

AF:

0.939

Gnomad4 FIN

AF:

0.983

Gnomad4 NFE

AF:

0.993

Gnomad4 OTH

AF:

0.939

Alfa

AF:

0.971

Hom.:

22790

Bravo

AF:

0.902

Asia WGS

AF:

0.855

AC:

2975

AN:

3478

EpiCase

AF:

0.991

EpiControl

AF:

0.991

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

SEMA3C-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 19, 2022

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

5.7

DANN

Benign

0.74

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