rs1880959

Positions:

• chr7-80798179-C-A
• chr7-80798179-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6 BP7 BA1

The ENST00000265361.8(SEMA3C):​c.1044G>T​(p.Val348=) 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 ENST00000265361.8 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.128

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

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/exons	MANE	Protein	UniProt
SEMA3C	NM_006379.5	c.1044G>T	p.Val348=	synonymous_variant	11/18	ENST00000265361.8	NP_006370.1
SEMA3C	NM_001350120.2	c.1098G>T	p.Val366=	synonymous_variant	11/18		NP_001337049.1
SEMA3C	NM_001350121.2	c.870G>T	p.Val290=	synonymous_variant	12/19		NP_001337050.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEMA3C	ENST00000265361.8	c.1044G>T	p.Val348=	synonymous_variant	11/18	1	NM_006379.5	ENSP00000265361	P1
SEMA3C	ENST00000419255.6	c.1044G>T	p.Val348=	synonymous_variant	11/18	2		ENSP00000411193	P1
SEMA3C	ENST00000475955.1	n.60G>T		non_coding_transcript_exon_variant	1/2	4
SEMA3C	ENST00000458729.5	c.*577G>T		3_prime_UTR_variant, NMD_transcript_variant	8/9	2		ENSP00000393825

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

GnomAD3 exomes AF: 0.0658 AC: 15852 AN: 240870 Hom.: 669 AF XY: 0.0661 AC XY: 8626 AN XY: 130544

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

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.: 32 AF XY: 0.0761 AC XY: 5662 AN XY: 74358

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: 68 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

SEMA3C-related disorder Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jan 03, 2023

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

Other links and lift over

dbSNP: rs1880959; hg19: chr7-80427495;