chr7-80798214-C-G

Variant names:

• chr7-80798214-C-G
• NM_006379.5:c.1009G>C
• SEMA3C p.Val337Leu

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_006379.5(SEMA3C):​c.1009G>C​(p.Val337Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V337M) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SEMA3C NM_006379.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.16
• 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: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.809

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.1009G>C	p.Val337Leu	missense	Exon 11 of 18	NP_006370.1	Q99985-1
	SEMA3C	NM_001350120.2		c.1063G>C	p.Val355Leu	missense	Exon 11 of 18	NP_001337049.1
	SEMA3C	NM_001350121.2		c.835G>C	p.Val279Leu	missense	Exon 12 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.1009G>C	p.Val337Leu	missense	Exon 11 of 18	ENSP00000265361.3	Q99985-1
	SEMA3C	ENST00000953788.1		c.1183G>C	p.Val395Leu	missense	Exon 13 of 20	ENSP00000623847.1
	SEMA3C	ENST00000953787.1		c.1126G>C	p.Val376Leu	missense	Exon 12 of 19	ENSP00000623846.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.65
BayesDel_addAF	Uncertain	0.098	D
BayesDel_noAF	Benign	-0.10
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.36	T
Eigen	Pathogenic	0.99
Eigen_PC	Pathogenic	0.92
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.97	D
M_CAP	Benign	0.051	D
MetaRNN	Pathogenic	0.81	D
MetaSVM	Uncertain	-0.13	T
MutationAssessor	Pathogenic	4.0	H
PhyloP100		6.2
PrimateAI	Uncertain	0.78	T
PROVEAN	Uncertain	-2.6	D
REVEL	Uncertain	0.44
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0050	D
Varity_R		0.87
gMVP		0.76
Mutation Taster		=54/46	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr7-80427530;