Variant 1-151133140-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_030913.6(SEMA6C):c.2137C>T(p.Arg713Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000572 in 1,560,024 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00043 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00059 ( 1 hom. )

Consequence

SEMA6C
NM_030913.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.19

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09115487).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEMA6C	NM_030913.6 link	c.2137C>T	p.Arg713Cys	missense_variant	19/19	ENST00000368914.8	NP_112175.2	Q9H3T2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SEMA6C	ENST00000368914.8 link	c.2137C>T	p.Arg713Cys	missense_variant	19/19	1	NM_030913.6	ENSP00000357910.3	Q9H3T2-1
SEMA6C	ENST00000368913.7 link	c.2233C>T	p.Arg745Cys	missense_variant	20/20	1		ENSP00000357909.3	Q9H3T2-3
SEMA6C	ENST00000341697.7 link	c.2137C>T	p.Arg713Cys	missense_variant	19/19	1		ENSP00000344148.3	Q9H3T2-1
SEMA6C	ENST00000368912.7 link	c.2113C>T	p.Arg705Cys	missense_variant	19/19	1		ENSP00000357908.3	Q9H3T2-2

Frequencies

GnomAD3 genomes

AF:

0.000435

AC:

AN:

151744

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000218

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000721

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:

0.000663

Gnomad OTH

AF:

0.000480

GnomAD3 exomes

AF:

0.000440

AC:

AN:

181810

Hom.:

AF XY:

0.000430

AC XY:

AN XY:

102420

show subpopulations

Gnomad AFR exome

AF:

0.000190

Gnomad AMR exome

AF:

0.00111

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000537

Gnomad OTH exome

AF:

0.000437

GnomAD4 exome

AF:

0.000587

AC:

826

AN:

1408168

Hom.:

Cov.:

AF XY:

0.000539

AC XY:

377

AN XY:

699968

show subpopulations

Gnomad4 AFR exome

AF:

0.000131

Gnomad4 AMR exome

AF:

0.00111

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000684

Gnomad4 OTH exome

AF:

0.000513

GnomAD4 genome

AF:

0.000435

AC:

AN:

151856

Hom.:

Cov.:

AF XY:

0.000458

AC XY:

AN XY:

74254

show subpopulations

Gnomad4 AFR

AF:

0.000217

Gnomad4 AMR

AF:

0.000720

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000663

Gnomad4 OTH

AF:

0.000475

Alfa

AF:

0.000416

Hom.:

Bravo

AF:

0.000468

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000315

AC:

ExAC

AF:

0.000279

AC:

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

Aug 10, 2021

The c.2233C>T (p.R745C) alteration is located in exon 20 (coding exon 18) of the SEMA6C gene. This alteration results from a C to T substitution at nucleotide position 2233, causing the arginine (R) at amino acid position 745 to be replaced by a cysteine (C). 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

0.14

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.38

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.33

.;.;T;T

Eigen

Benign

0.17

Eigen_PC

Benign

0.13

FATHMM_MKL

Uncertain

0.88

LIST_S2

Uncertain

0.93

D;D;.;D

M_CAP

Uncertain

0.21

MetaRNN

Benign

0.091

T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.8

.;.;L;L

PrimateAI

Pathogenic

0.81

PROVEAN

Uncertain

-3.0

D;D;D;D

REVEL

Benign

0.23

Sift

Uncertain

0.0030

D;D;D;D

Sift4G

Uncertain

0.0040

D;D;D;D

Polyphen

1.0

D;D;D;D

Vest4

0.28

MVP

0.54

MPC

1.3

ClinPred

0.21

GERP RS

2.8

Varity_R

0.19

gMVP

0.32

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