Variant 7-80745026-A-G 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.2124T>C(p.Tyr708=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.98 in 1,614,054 control chromosomes in the GnomAD database, including 777,793 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.93 ( 66717 hom., cov: 32)

Exomes 𝑓: 0.99 ( 711076 hom. )

Consequence

SEMA3C
NM_006379.5 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 2.77

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=-0.61).

BP6

Variant 7-80745026-A-G is Benign according to our data. Variant chr7-80745026-A-G is described in ClinVar as [Benign]. Clinvar id is 3060435.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=2.77 with no splicing effect.

BA1

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
SEMA3C	NM_006379.5 linkuse as main transcript	c.2124T>C	p.Tyr708=	synonymous_variant	18/18	ENST00000265361.8	NP_006370.1
SEMA3C	NM_001350120.2 linkuse as main transcript	c.2178T>C	p.Tyr726=	synonymous_variant	18/18		NP_001337049.1
SEMA3C	NM_001350121.2 linkuse as main transcript	c.1950T>C	p.Tyr650=	synonymous_variant	19/19		NP_001337050.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEMA3C	ENST00000265361.8 linkuse as main transcript	c.2124T>C	p.Tyr708=	synonymous_variant	18/18	1	NM_006379.5	ENSP00000265361	P1	Q99985-1
SEMA3C	ENST00000419255.6 linkuse as main transcript	c.2124T>C	p.Tyr708=	synonymous_variant	18/18	2		ENSP00000411193	P1	Q99985-1

Frequencies

GnomAD3 genomes

AF:

0.931

AC:

141627

AN:

152114

Hom.:

66682

Cov.:

show subpopulations

Gnomad AFR

AF:

0.777

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.976

Gnomad ASJ

AF:

0.969

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

0.952

Gnomad FIN

AF:

0.997

Gnomad MID

AF:

0.972

Gnomad NFE

AF:

0.994

Gnomad OTH

AF:

0.956

GnomAD3 exomes

AF:

0.973

AC:

244449

AN:

251216

Hom.:

119313

AF XY:

0.975

AC XY:

132422

AN XY:

135756

show subpopulations

Gnomad AFR exome

AF:

0.776

Gnomad AMR exome

AF:

0.985

Gnomad ASJ exome

AF:

0.975

Gnomad EAS exome

AF:

1.00

Gnomad SAS exome

AF:

0.959

Gnomad FIN exome

AF:

0.996

Gnomad NFE exome

AF:

0.992

Gnomad OTH exome

AF:

0.981

GnomAD4 exome

AF:

0.986

AC:

1440790

AN:

1461824

Hom.:

711076

Cov.:

AF XY:

0.985

AC XY:

716474

AN XY:

727216

show subpopulations

Gnomad4 AFR exome

AF:

0.768

Gnomad4 AMR exome

AF:

0.983

Gnomad4 ASJ exome

AF:

0.973

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

0.959

Gnomad4 FIN exome

AF:

0.997

Gnomad4 NFE exome

AF:

0.994

Gnomad4 OTH exome

AF:

0.975

GnomAD4 genome

AF:

0.931

AC:

141718

AN:

152230

Hom.:

66717

Cov.:

AF XY:

0.932

AC XY:

69399

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.777

Gnomad4 AMR

AF:

0.976

Gnomad4 ASJ

AF:

0.969

Gnomad4 EAS

AF:

1.00

Gnomad4 SAS

AF:

0.951

Gnomad4 FIN

AF:

0.997

Gnomad4 NFE

AF:

0.994

Gnomad4 OTH

AF:

0.956

Alfa

AF:

0.962

Hom.:

38851

Bravo

AF:

0.925

Asia WGS

AF:

0.970

AC:

3372

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

-0.61

CADD

Benign

7.0

DANN

Benign

0.48

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