Variant rs1949972 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.2028A>G(p.Pro676=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.968 in 1,613,868 control chromosomes in the GnomAD database, including 759,539 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.90 ( 63026 hom., cov: 31)

Exomes 𝑓: 0.97 ( 696513 hom. )

Consequence

SEMA3C
NM_006379.5 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.930

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=-0.81).

BP6

Variant 7-80745122-T-C is Benign according to our data. Variant chr7-80745122-T-C is described in ClinVar as [Benign]. Clinvar id is 3058982.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-0.93 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.986 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.2028A>G	p.Pro676=	synonymous_variant	18/18	ENST00000265361.8	NP_006370.1
SEMA3C	NM_001350120.2 linkuse as main transcript	c.2082A>G	p.Pro694=	synonymous_variant	18/18		NP_001337049.1
SEMA3C	NM_001350121.2 linkuse as main transcript	c.1854A>G	p.Pro618=	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.2028A>G	p.Pro676=	synonymous_variant	18/18	1	NM_006379.5	ENSP00000265361	P1	Q99985-1
SEMA3C	ENST00000419255.6 linkuse as main transcript	c.2028A>G	p.Pro676=	synonymous_variant	18/18	2		ENSP00000411193	P1	Q99985-1

Frequencies

GnomAD3 genomes

AF:

0.903

AC:

137165

AN:

151974

Hom.:

63008

Cov.:

show subpopulations

Gnomad AFR

AF:

0.727

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.931

Gnomad ASJ

AF:

0.965

Gnomad EAS

AF:

0.764

Gnomad SAS

AF:

0.941

Gnomad FIN

AF:

0.983

Gnomad MID

AF:

0.965

Gnomad NFE

AF:

0.992

Gnomad OTH

AF:

0.934

GnomAD3 exomes

AF:

0.940

AC:

236083

AN:

251206

Hom.:

111829

AF XY:

0.947

AC XY:

128537

AN XY:

135756

show subpopulations

Gnomad AFR exome

AF:

0.728

Gnomad AMR exome

AF:

0.911

Gnomad ASJ exome

AF:

0.970

Gnomad EAS exome

AF:

0.765

Gnomad SAS exome

AF:

0.955

Gnomad FIN exome

AF:

0.982

Gnomad NFE exome

AF:

0.991

Gnomad OTH exome

AF:

0.958

GnomAD4 exome

AF:

0.975

AC:

1424585

AN:

1461776

Hom.:

696513

Cov.:

AF XY:

0.975

AC XY:

708913

AN XY:

727196

show subpopulations

Gnomad4 AFR exome

AF:

0.717

Gnomad4 AMR exome

AF:

0.911

Gnomad4 ASJ exome

AF:

0.969

Gnomad4 EAS exome

AF:

0.799

Gnomad4 SAS exome

AF:

0.954

Gnomad4 FIN exome

AF:

0.984

Gnomad4 NFE exome

AF:

0.994

Gnomad4 OTH exome

AF:

0.952

GnomAD4 genome

AF:

0.902

AC:

137233

AN:

152092

Hom.:

63026

Cov.:

AF XY:

0.903

AC XY:

67097

AN XY:

74326

show subpopulations

Gnomad4 AFR

AF:

0.727

Gnomad4 AMR

AF:

0.931

Gnomad4 ASJ

AF:

0.965

Gnomad4 EAS

AF:

0.763

Gnomad4 SAS

AF:

0.940

Gnomad4 FIN

AF:

0.983

Gnomad4 NFE

AF:

0.992

Gnomad4 OTH

AF:

0.935

Alfa

AF:

0.972

Hom.:

136914

Bravo

AF:

0.891

Asia WGS

AF:

0.859

AC:

2989

AN:

3478

EpiCase

AF:

0.990

EpiControl

AF:

0.989

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

-0.81

CADD

Benign

0.85

DANN

Benign

0.64

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