dbSNP rs17275986: SEMA3C:p.Tyr429Tyr (chr7-80789373-A-G) – ACMG Classification: Benign (-14 pts)

Variant summary

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

The NM_006379.5(SEMA3C):c.1287T>C(p.Tyr429Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 1,613,682 control chromosomes in the GnomAD database, including 29,215 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.15 ( 2073 hom., cov: 32)

Exomes 𝑓: 0.19 ( 27142 hom. )

Consequence

SEMA3C
NM_006379.5 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.45

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 7-80789373-A-G is Benign according to our data. Variant chr7-80789373-A-G is described in ClinVar as [Benign]. Clinvar id is 3060714.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=1.45 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.2 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEMA3C	NM_006379.5 link	c.1287T>C	p.Tyr429Tyr	synonymous_variant	Exon 12 of 18	ENST00000265361.8	NP_006370.1	Q99985-1
SEMA3C	NM_001350120.2 link	c.1341T>C	p.Tyr447Tyr	synonymous_variant	Exon 12 of 18		NP_001337049.1
SEMA3C	NM_001350121.2 link	c.1113T>C	p.Tyr371Tyr	synonymous_variant	Exon 13 of 19		NP_001337050.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEMA3C	ENST00000265361.8 link	c.1287T>C	p.Tyr429Tyr	synonymous_variant	Exon 12 of 18	1	NM_006379.5	ENSP00000265361.3		Q99985-1
SEMA3C	ENST00000419255.6 link	c.1287T>C	p.Tyr429Tyr	synonymous_variant	Exon 12 of 18	2		ENSP00000411193.2		Q99985-1

Frequencies

GnomAD3 genomes

AF:

0.154

AC:

23355

AN:

152012

Hom.:

2072

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0806

Gnomad AMI

AF:

0.195

Gnomad AMR

AF:

0.141

Gnomad ASJ

AF:

0.102

Gnomad EAS

AF:

0.0897

Gnomad SAS

AF:

0.120

Gnomad FIN

AF:

0.206

Gnomad MID

AF:

0.0949

Gnomad NFE

AF:

0.203

Gnomad OTH

AF:

0.132

GnomAD3 exomes

AF:

0.157

AC:

39483

AN:

251276

Hom.:

3534

AF XY:

0.160

AC XY:

21687

AN XY:

135798

show subpopulations

Gnomad AFR exome

AF:

0.0773

Gnomad AMR exome

AF:

0.105

Gnomad ASJ exome

AF:

0.110

Gnomad EAS exome

AF:

0.0911

Gnomad SAS exome

AF:

0.113

Gnomad FIN exome

AF:

0.203

Gnomad NFE exome

AF:

0.203

Gnomad OTH exome

AF:

0.151

GnomAD4 exome

AF:

0.188

AC:

274218

AN:

1461552

Hom.:

27142

Cov.:

AF XY:

0.186

AC XY:

135062

AN XY:

727088

show subpopulations

Gnomad4 AFR exome

AF:

0.0725

Gnomad4 AMR exome

AF:

0.108

Gnomad4 ASJ exome

AF:

0.109

Gnomad4 EAS exome

AF:

0.0751

Gnomad4 SAS exome

AF:

0.115

Gnomad4 FIN exome

AF:

0.204

Gnomad4 NFE exome

AF:

0.207

Gnomad4 OTH exome

AF:

0.166

GnomAD4 genome

AF:

0.154

AC:

23355

AN:

152130

Hom.:

2073

Cov.:

AF XY:

0.154

AC XY:

11441

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.0805

Gnomad4 AMR

AF:

0.140

Gnomad4 ASJ

AF:

0.102

Gnomad4 EAS

AF:

0.0899

Gnomad4 SAS

AF:

0.119

Gnomad4 FIN

AF:

0.206

Gnomad4 NFE

AF:

0.203

Gnomad4 OTH

AF:

0.133

Alfa

AF:

0.181

Hom.:

6530

Bravo

AF:

0.141

Asia WGS

AF:

0.112

AC:

388

AN:

3478

EpiCase

AF:

0.190

EpiControl

AF:

0.185

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

SEMA3C-related disorder

Benign:1

Aug 19, 2022

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

-0.56

CADD

Benign

7.1

DANN

Benign

0.38

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