chr7-80798179-C-A

Variant names:

• chr7-80798179-C-A
• rs1880959
• NM_006379.5:c.1044G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Moderate BP6 BP7 BA1

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
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.128
• Publications: 14 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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	c.1044G>T	p.Val348Val	synonymous_variant	Exon 11 of 18	ENST00000265361.8	NP_006370.1
SEMA3C	NM_001350120.2	c.1098G>T	p.Val366Val	synonymous_variant	Exon 11 of 18		NP_001337049.1
SEMA3C	NM_001350121.2	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	c.1044G>T	p.Val348Val	synonymous_variant	Exon 11 of 18	1	NM_006379.5	ENSP00000265361.3

Frequencies

GnomAD3 genomes AF: 0.0795 AC: 12086 AN: 151996 Hom.: 501 Cov.: 32

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

GnomAD2 exomes AF: 0.0658 AC: 15852 AN: 240870 AF XY: 0.0661

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 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.: 31 AF XY: 0.0841 AC XY: 60782 AN XY: 722816

African (AFR) AF: 0.0739 AC: 2427 AN: 32848

American (AMR) AF: 0.0356 AC: 1539 AN: 43250

Ashkenazi Jewish (ASJ) AF: 0.0665 AC: 1728 AN: 25974

East Asian (EAS) AF: 0.000896 AC: 35 AN: 39072

South Asian (SAS) AF: 0.0349 AC: 2958 AN: 84852

European-Finnish (FIN) AF: 0.0709 AC: 3779 AN: 53324

Middle Eastern (MID) AF: 0.0744 AC: 427 AN: 5736

European-Non Finnish (NFE) AF: 0.0968 AC: 107202 AN: 1107964

Other (OTH) AF: 0.0766 AC: 4597 AN: 60006

GnomAD4 genome AF: 0.0795 AC: 12097 AN: 152112 Hom.: 503 Cov.: 32 AF XY: 0.0761 AC XY: 5662 AN XY: 74358

African (AFR) AF: 0.0799 AC: 3313 AN: 41488

American (AMR) AF: 0.0531 AC: 811 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.0674 AC: 234 AN: 3472

East Asian (EAS) AF: 0.00213 AC: 11 AN: 5176

South Asian (SAS) AF: 0.0299 AC: 144 AN: 4822

European-Finnish (FIN) AF: 0.0666 AC: 705 AN: 10584

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.0971 AC: 6600 AN: 67980

Other (OTH) AF: 0.0801 AC: 169 AN: 2110

Alfa AF: 0.0907 Hom.: 1035

Bravo AF: 0.0793

Asia WGS AF: 0.0190 AC: 68 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

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
PhyloP100		0.13
Mutation Taster		=92/8	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1880959; hg19: chr7-80427495;