dbSNP rs1880959: SEMA3C:p.Val348Val (chr7-80798179-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6BP7BA1

The NM_006379.5(SEMA3C):c.1044G>T(p.Val348Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0852 in 1,605,138 control chromosomes in the GnomAD database, including 6,331 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.080 ( 503 hom., cov: 32)

Exomes 𝑓: 0.086 ( 5828 hom. )

Consequence

SEMA3C
NM_006379.5 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.128

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.19).

BP6

Variant 7-80798179-C-A is Benign according to our data. Variant chr7-80798179-C-A is described in ClinVar as [Benign]. Clinvar id is 3059373.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=0.128 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0951 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEMA3C	NM_006379.5 link	c.1044G>T	p.Val348Val	synonymous_variant	Exon 11 of 18	ENST00000265361.8	NP_006370.1	Q99985-1
SEMA3C	NM_001350120.2 link	c.1098G>T	p.Val366Val	synonymous_variant	Exon 11 of 18		NP_001337049.1
SEMA3C	NM_001350121.2 link	c.870G>T	p.Val290Val	synonymous_variant	Exon 12 of 19		NP_001337050.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEMA3C	ENST00000265361.8 link	c.1044G>T	p.Val348Val	synonymous_variant	Exon 11 of 18	1	NM_006379.5	ENSP00000265361.3		Q99985-1

Frequencies

GnomAD3 genomes

AF:

0.0795

AC:

12086

AN:

151996

Hom.:

501

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0797

Gnomad AMI

AF:

0.0965

Gnomad AMR

AF:

0.0532

Gnomad ASJ

AF:

0.0674

Gnomad EAS

AF:

0.00212

Gnomad SAS

AF:

0.0296

Gnomad FIN

AF:

0.0666

Gnomad MID

AF:

0.0791

Gnomad NFE

AF:

0.0971

Gnomad OTH

AF:

0.0809

GnomAD3 exomes

AF:

0.0658

AC:

15852

AN:

240870

Hom.:

669

AF XY:

0.0661

AC XY:

8626

AN XY:

130544

show subpopulations

Gnomad AFR exome

AF:

0.0731

Gnomad AMR exome

AF:

0.0323

Gnomad ASJ exome

AF:

0.0663

Gnomad EAS exome

AF:

0.00160

Gnomad SAS exome

AF:

0.0323

Gnomad FIN exome

AF:

0.0696

Gnomad NFE exome

AF:

0.0927

Gnomad OTH exome

AF:

0.0672

GnomAD4 exome

AF:

0.0858

AC:

124692

AN:

1453026

Hom.:

5828

Cov.:

AF XY:

0.0841

AC XY:

60782

AN XY:

722816

show subpopulations

Gnomad4 AFR exome

AF:

0.0739

Gnomad4 AMR exome

AF:

0.0356

Gnomad4 ASJ exome

AF:

0.0665

Gnomad4 EAS exome

AF:

0.000896

Gnomad4 SAS exome

AF:

0.0349

Gnomad4 FIN exome

AF:

0.0709

Gnomad4 NFE exome

AF:

0.0968

Gnomad4 OTH exome

AF:

0.0766

GnomAD4 genome

AF:

0.0795

AC:

12097

AN:

152112

Hom.:

503

Cov.:

AF XY:

0.0761

AC XY:

5662

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.0799

Gnomad4 AMR

AF:

0.0531

Gnomad4 ASJ

AF:

0.0674

Gnomad4 EAS

AF:

0.00213

Gnomad4 SAS

AF:

0.0299

Gnomad4 FIN

AF:

0.0666

Gnomad4 NFE

AF:

0.0971

Gnomad4 OTH

AF:

0.0801

Alfa

AF:

0.0905

Hom.:

898

Bravo

AF:

0.0793

Asia WGS

AF:

0.0190

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

SEMA3C-related disorder

Benign:1

Jan 03, 2023

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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

-0.19

CADD

Benign

6.7

DANN

Benign

0.77

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