rs2272351

Variant names:

• chr7-80749003-G-C
• rs2272351
• NM_006379.5:c.1737C>G

Your query was ambiguous. Multiple possible variants found:

• chr7-80749003-G-C
• chr7-80749003-G-A
• chr7-80749003-G-T

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.1737C>G​(p.Val579Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.97 in 1,611,996 control chromosomes in the GnomAD database, including 761,424 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.91 (64175 hom., cov: 31)
  • Exomes 𝑓: 0.98 (697249 hom.)
• Consequence: SEMA3C NM_006379.5 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.413
• Publications: 22 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=-0.56).
• BP6: Variant 7-80749003-G-C is Benign according to our data. Variant chr7-80749003-G-C is described in ClinVar as Benign. ClinVar VariationId is 3060860.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=0.413 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.987 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006379.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEMA3C	NM_006379.5	MANE Select	c.1737C>G	p.Val579Val	synonymous	Exon 17 of 18	NP_006370.1	Q99985-1
	SEMA3C	NM_001350120.2		c.1791C>G	p.Val597Val	synonymous	Exon 17 of 18	NP_001337049.1
	SEMA3C	NM_001350121.2		c.1563C>G	p.Val521Val	synonymous	Exon 18 of 19	NP_001337050.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEMA3C	ENST00000265361.8	TSL:1 MANE Select	c.1737C>G	p.Val579Val	synonymous	Exon 17 of 18	ENSP00000265361.3	Q99985-1
	SEMA3C	ENST00000953788.1		c.1911C>G	p.Val637Val	synonymous	Exon 19 of 20	ENSP00000623847.1
	SEMA3C	ENST00000953787.1		c.1854C>G	p.Val618Val	synonymous	Exon 18 of 19	ENSP00000623846.1

Frequencies

GnomAD3 genomes AF: 0.913 AC: 138705 AN: 152004 Hom.: 64165 Cov.: 31

Gnomad AFR AF: 0.760

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.936

Gnomad ASJ AF: 0.975

Gnomad EAS AF: 0.763

Gnomad SAS AF: 0.939

Gnomad FIN AF: 0.983

Gnomad MID AF: 0.968

Gnomad NFE AF: 0.993

Gnomad OTH AF: 0.938

GnomAD2 exomes AF: 0.942 AC: 234834 AN: 249162 AF XY: 0.949

Gnomad AFR exome AF: 0.760

Gnomad AMR exome AF: 0.912

Gnomad ASJ exome AF: 0.978

Gnomad EAS exome AF: 0.764

Gnomad FIN exome AF: 0.983

Gnomad NFE exome AF: 0.992

Gnomad OTH exome AF: 0.962

GnomAD4 exome AF: 0.976 AC: 1424727 AN: 1459874 Hom.: 697249 Cov.: 38 AF XY: 0.976 AC XY: 708842 AN XY: 726230

African (AFR) AF: 0.752 AC: 25056 AN: 33324

American (AMR) AF: 0.913 AC: 40488 AN: 44332

Ashkenazi Jewish (ASJ) AF: 0.977 AC: 25409 AN: 26016

East Asian (EAS) AF: 0.799 AC: 31666 AN: 39638

South Asian (SAS) AF: 0.953 AC: 81871 AN: 85914

European-Finnish (FIN) AF: 0.984 AC: 52529 AN: 53382

Middle Eastern (MID) AF: 0.946 AC: 5443 AN: 5752

European-Non Finnish (NFE) AF: 0.994 AC: 1104682 AN: 1111204

Other (OTH) AF: 0.955 AC: 57583 AN: 60312

GnomAD4 genome AF: 0.912 AC: 138766 AN: 152122 Hom.: 64175 Cov.: 31 AF XY: 0.912 AC XY: 67840 AN XY: 74366

African (AFR) AF: 0.759 AC: 31457 AN: 41420

American (AMR) AF: 0.935 AC: 14289 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.975 AC: 3383 AN: 3470

East Asian (EAS) AF: 0.762 AC: 3932 AN: 5160

South Asian (SAS) AF: 0.939 AC: 4524 AN: 4818

European-Finnish (FIN) AF: 0.983 AC: 10438 AN: 10616

Middle Eastern (MID) AF: 0.963 AC: 283 AN: 294

European-Non Finnish (NFE) AF: 0.993 AC: 67563 AN: 68042

Other (OTH) AF: 0.939 AC: 1985 AN: 2114

Alfa AF: 0.971 Hom.: 22790

Bravo AF: 0.902

Asia WGS AF: 0.855 AC: 2975 AN: 3478

EpiCase AF: 0.991

EpiControl AF: 0.991

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	SEMA3C-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	5.7
DANN	Benign	0.74
PhyloP100		0.41
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: rs2272351; hg19: chr7-80378319; COSMIC: COSV108090209;