Variant 1-151136113-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_030913.6(SEMA6C):c.1157G>A(p.Arg386Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000122 in 1,613,834 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00013 ( 0 hom. )

Consequence

SEMA6C
NM_030913.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.648

Variant links:

Genes affected

SEMA6C (HGNC:10740): (semaphorin 6C) This gene encodes a member of the semaphorin family. Semaphorins represent important molecular signals controlling multiple aspects of the cellular response that follows CNS injury, and thus may play an important role in neural regeneration. [provided by RefSeq, May 2010]

SEMA6C links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.04551503).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEMA6C	NM_030913.6 link	c.1157G>A	p.Arg386Gln	missense_variant	13/19	ENST00000368914.8	NP_112175.2	Q9H3T2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SEMA6C	ENST00000368914.8 link	c.1157G>A	p.Arg386Gln	missense_variant	13/19	1	NM_030913.6	ENSP00000357910.3	Q9H3T2-1
SEMA6C	ENST00000368913.7 link	c.1157G>A	p.Arg386Gln	missense_variant	13/20	1		ENSP00000357909.3	Q9H3T2-3
SEMA6C	ENST00000341697.7 link	c.1157G>A	p.Arg386Gln	missense_variant	13/19	1		ENSP00000344148.3	Q9H3T2-1
SEMA6C	ENST00000368912.7 link	c.1037G>A	p.Arg346Gln	missense_variant	12/19	1		ENSP00000357908.3	Q9H3T2-2

Frequencies

GnomAD3 genomes

AF:

0.0000921

AC:

AN:

151986

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000191

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000143

AC:

AN:

251414

Hom.:

AF XY:

0.000140

AC XY:

AN XY:

135884

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000174

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.000255

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000125

AC:

183

AN:

1461848

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

727228

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.000157

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.0000374

Gnomad4 NFE exome

AF:

0.000152

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000921

AC:

AN:

151986

Hom.:

Cov.:

AF XY:

0.0000808

AC XY:

AN XY:

74218

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000191

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000160

Hom.:

Bravo

AF:

0.000121

ExAC

AF:

0.000157

AC:

EpiCase

AF:

0.000218

EpiControl

AF:

0.000356

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 14, 2021

The c.1157G>A (p.R386Q) alteration is located in exon 13 (coding exon 11) of the SEMA6C gene. This alteration results from a G to A substitution at nucleotide position 1157, causing the arginine (R) at amino acid position 386 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.76

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.038

.;.;T;T

Eigen

Benign

-0.56

Eigen_PC

Benign

-0.46

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.83

T;T;.;T

M_CAP

Benign

0.0048

MetaRNN

Benign

0.046

T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.68

N;.;N;N

PrimateAI

Benign

0.23

PROVEAN

Benign

-0.020

N;N;N;N

REVEL

Benign

0.060

Sift

Benign

0.39

T;T;T;T

Sift4G

Benign

0.16

T;T;T;T

Polyphen

0.029

B;B;B;B

Vest4

0.29

MVP

0.31

MPC

0.81

ClinPred

0.087

GERP RS

3.5

Varity_R

0.051

gMVP

0.49

Splicing

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over