chr7-80745122-T-C

Variant names:

• chr7-80745122-T-C
• rs1949972
• NM_006379.5:c.2028A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_006379.5(SEMA3C):​c.2028A>G​(p.Pro676Pro) 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
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.930
• Publications: 20 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 -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 VariationId 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 rank	MANE	Protein	UniProt
SEMA3C	NM_006379.5	c.2028A>G	p.Pro676Pro	synonymous_variant	Exon 18 of 18	ENST00000265361.8	NP_006370.1
SEMA3C	NM_001350120.2	c.2082A>G	p.Pro694Pro	synonymous_variant	Exon 18 of 18		NP_001337049.1
SEMA3C	NM_001350121.2	c.1854A>G	p.Pro618Pro	synonymous_variant	Exon 19 of 19		NP_001337050.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEMA3C	ENST00000265361.8	c.2028A>G	p.Pro676Pro	synonymous_variant	Exon 18 of 18	1	NM_006379.5	ENSP00000265361.3
SEMA3C	ENST00000419255.6	c.2028A>G	p.Pro676Pro	synonymous_variant	Exon 18 of 18	2		ENSP00000411193.2

Frequencies

GnomAD3 genomes AF: 0.903 AC: 137165 AN: 151974 Hom.: 63008 Cov.: 31

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

GnomAD2 exomes AF: 0.940 AC: 236083 AN: 251206 AF XY: 0.947

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 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.: 61 AF XY: 0.975 AC XY: 708913 AN XY: 727196

African (AFR) AF: 0.717 AC: 23999 AN: 33464

American (AMR) AF: 0.911 AC: 40724 AN: 44686

Ashkenazi Jewish (ASJ) AF: 0.969 AC: 25313 AN: 26130

East Asian (EAS) AF: 0.799 AC: 31727 AN: 39698

South Asian (SAS) AF: 0.954 AC: 82315 AN: 86258

European-Finnish (FIN) AF: 0.984 AC: 52539 AN: 53412

Middle Eastern (MID) AF: 0.942 AC: 5436 AN: 5768

European-Non Finnish (NFE) AF: 0.994 AC: 1105047 AN: 1111966

Other (OTH) AF: 0.952 AC: 57485 AN: 60394

GnomAD4 genome AF: 0.902 AC: 137233 AN: 152092 Hom.: 63026 Cov.: 31 AF XY: 0.903 AC XY: 67097 AN XY: 74326

African (AFR) AF: 0.727 AC: 30142 AN: 41460

American (AMR) AF: 0.931 AC: 14204 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.965 AC: 3347 AN: 3470

East Asian (EAS) AF: 0.763 AC: 3917 AN: 5134

South Asian (SAS) AF: 0.940 AC: 4536 AN: 4826

European-Finnish (FIN) AF: 0.983 AC: 10423 AN: 10606

Middle Eastern (MID) AF: 0.959 AC: 282 AN: 294

European-Non Finnish (NFE) AF: 0.992 AC: 67495 AN: 68014

Other (OTH) AF: 0.935 AC: 1975 AN: 2112

Alfa AF: 0.962 Hom.: 280712

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

Submissions by phenotype

SEMA3C-related disorder Benign:1

Jul 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	-0.81
CADD	Benign	0.85
DANN	Benign	0.64
PhyloP100		-0.93
Mutation Taster		=100/0	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: rs1949972; hg19: chr7-80374438; COSMIC: COSV108090208;