dbSNP rs552613702: SEMA3C:p.Arg739Leu (chr7-80744934-C-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_006379.5(SEMA3C):c.2216G>T(p.Arg739Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,764 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R739Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

SEMA3C
NM_006379.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.74

Publications

0 publications found

Variant links:

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]

SEMA3C links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SEMA3C	NM_006379.5	MANE Select	c.2216G>T	p.Arg739Leu	missense	Exon 18 of 18	NP_006370.1	Q99985-1
SEMA3C	NM_001350120.2		c.2270G>T	p.Arg757Leu	missense	Exon 18 of 18	NP_001337049.1
SEMA3C	NM_001350121.2		c.2042G>T	p.Arg681Leu	missense	Exon 19 of 19	NP_001337050.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SEMA3C	ENST00000265361.8	TSL:1 MANE Select	c.2216G>T	p.Arg739Leu	missense	Exon 18 of 18	ENSP00000265361.3	Q99985-1
SEMA3C	ENST00000953788.1		c.2390G>T	p.Arg797Leu	missense	Exon 20 of 20	ENSP00000623847.1
SEMA3C	ENST00000953787.1		c.2333G>T	p.Arg778Leu	missense	Exon 19 of 19	ENSP00000623846.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461764

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727186

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33464

American (AMR)

AF:

0.00

AC:

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53414

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111936

Other (OTH)

AF:

0.0000166

AC:

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.74

BayesDel_addAF

Uncertain

0.080

BayesDel_noAF

Benign

-0.12

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.54

Eigen

Uncertain

0.57

Eigen_PC

Uncertain

0.62

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.95

M_CAP

Benign

0.063

MetaRNN

Uncertain

0.52

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.8

PhyloP100

5.7

PrimateAI

Uncertain

0.70

PROVEAN

Uncertain

-3.3

REVEL

Uncertain

0.32

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.014

Polyphen

0.96

Vest4

0.53

MVP

0.46

MPC

0.69

ClinPred

1.0

GERP RS

5.6

Varity_R

0.51

gMVP

0.45

Mutation Taster

=33/67

disease causing

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over