rs1949972

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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 -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 id 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

GnomAD3 exomes AF: 0.940 AC: 236083 AN: 251206 Hom.: 111829 AF XY: 0.947 AC XY: 128537 AN XY: 135756

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 SAS exome AF: 0.955

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

Gnomad4 AFR exome AF: 0.717

Gnomad4 AMR exome AF: 0.911

Gnomad4 ASJ exome AF: 0.969

Gnomad4 EAS exome AF: 0.799

Gnomad4 SAS exome AF: 0.954

Gnomad4 FIN exome AF: 0.984

Gnomad4 NFE exome AF: 0.994

Gnomad4 OTH exome AF: 0.952

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

Gnomad4 AFR AF: 0.727

Gnomad4 AMR AF: 0.931

Gnomad4 ASJ AF: 0.965

Gnomad4 EAS AF: 0.763

Gnomad4 SAS AF: 0.940

Gnomad4 FIN AF: 0.983

Gnomad4 NFE AF: 0.992

Gnomad4 OTH AF: 0.935

Alfa AF: 0.972 Hom.: 136914

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

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: rs1949972; hg19: chr7-80374438;