Genetic Variant SEMA3C:c.1842+39A>G (chr7-80748859-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_006379.5(SEMA3C):c.1842+39A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.99 in 1,575,270 control chromosomes in the GnomAD database, including 772,989 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.95 ( 68739 hom., cov: 31)

Exomes 𝑓: 0.99 ( 704250 hom. )

Consequence

SEMA3C
NM_006379.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.67

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 made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
SEMA3C	NM_006379.5 link	c.1842+39A>G	intron_variant	Intron 17 of 17	ENST00000265361.8	NP_006370.1	Q99985-1
SEMA3C	NM_001350120.2 link	c.1896+39A>G	intron_variant	Intron 17 of 17		NP_001337049.1
SEMA3C	NM_001350121.2 link	c.1668+39A>G	intron_variant	Intron 18 of 18		NP_001337050.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEMA3C	ENST00000265361.8 link	c.1842+39A>G		intron_variant	Intron 17 of 17	1	NM_006379.5	ENSP00000265361.3		Q99985-1
SEMA3C	ENST00000419255.6 link	c.1842+39A>G		intron_variant	Intron 17 of 17	2		ENSP00000411193.2		Q99985-1

Frequencies

GnomAD3 genomes

AF:

0.947

AC:

143938

AN:

152044

Hom.:

68695

Cov.:

show subpopulations

Gnomad AFR

AF:

0.813

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.985

Gnomad ASJ

AF:

0.992

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

0.999

Gnomad FIN

AF:

1.00

Gnomad MID

AF:

0.997

Gnomad NFE

AF:

0.999

Gnomad OTH

AF:

0.971

GnomAD3 exomes

AF:

0.985

AC:

218046

AN:

221412

Hom.:

107626

AF XY:

0.989

AC XY:

117988

AN XY:

119316

show subpopulations

Gnomad AFR exome

AF:

0.810

Gnomad AMR exome

AF:

0.991

Gnomad ASJ exome

AF:

0.995

Gnomad EAS exome

AF:

1.00

Gnomad SAS exome

AF:

1.00

Gnomad FIN exome

AF:

1.00

Gnomad NFE exome

AF:

0.999

Gnomad OTH exome

AF:

0.994

GnomAD4 exome

AF:

0.994

AC:

1415109

AN:

1423108

Hom.:

704250

Cov.:

AF XY:

0.995

AC XY:

702392

AN XY:

705908

show subpopulations

Gnomad4 AFR exome

AF:

0.804

Gnomad4 AMR exome

AF:

0.990

Gnomad4 ASJ exome

AF:

0.995

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

0.999

Gnomad4 FIN exome

AF:

1.00

Gnomad4 NFE exome

AF:

1.00

Gnomad4 OTH exome

AF:

0.987

GnomAD4 genome

AF:

0.947

AC:

144039

AN:

152162

Hom.:

68739

Cov.:

AF XY:

0.949

AC XY:

70579

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.813

Gnomad4 AMR

AF:

0.985

Gnomad4 ASJ

AF:

0.992

Gnomad4 EAS

AF:

1.00

Gnomad4 SAS

AF:

0.999

Gnomad4 FIN

AF:

1.00

Gnomad4 NFE

AF:

0.999

Gnomad4 OTH

AF:

0.972

Alfa

AF:

0.991

Hom.:

63500

Bravo

AF:

0.941

Asia WGS

AF:

0.991

AC:

3446

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.59

DANN

Benign

0.36

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over