rs1267930958

Variant names:

• chr7-80745011-C-T
• rs1267930958
• NM_006379.5:c.2139G>A

Your query was ambiguous. Multiple possible variants found:

• chr7-80745011-C-T
• chr7-80745011-C-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6 BP7

The NM_006379.5(SEMA3C):​c.2139G>A​(p.Arg713Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SEMA3C NM_006379.5 synonymous
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.253
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BP6: Variant 7-80745011-C-T is Benign according to our data. Variant chr7-80745011-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3357238.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=0.253 with no splicing effect.

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.2139G>A	p.Arg713Arg	synonymous	Exon 18 of 18	NP_006370.1	Q99985-1
	SEMA3C	NM_001350120.2		c.2193G>A	p.Arg731Arg	synonymous	Exon 18 of 18	NP_001337049.1
	SEMA3C	NM_001350121.2		c.1965G>A	p.Arg655Arg	synonymous	Exon 19 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.2139G>A	p.Arg713Arg	synonymous	Exon 18 of 18	ENSP00000265361.3	Q99985-1
	SEMA3C	ENST00000953788.1		c.2313G>A	p.Arg771Arg	synonymous	Exon 20 of 20	ENSP00000623847.1
	SEMA3C	ENST00000953787.1		c.2256G>A	p.Arg752Arg	synonymous	Exon 19 of 19	ENSP00000623846.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely 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	-0.41
CADD	Benign	6.0
DANN	Benign	0.53
PhyloP100		0.25

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: rs1267930958; hg19: chr7-80374327;