Variant 1-151133151-A-G 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.2126T>C(p.Val709Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000902 in 1,552,398 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 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000078 ( 0 hom. )

Consequence

SEMA6C
NM_030913.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.40

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=0.026262581).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SEMA6C	NM_030913.6 linkuse as main transcript	c.2126T>C	p.Val709Ala	missense_variant	19/19	ENST00000368914.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEMA6C	ENST00000368914.8 linkuse as main transcript	c.2126T>C	p.Val709Ala	missense_variant	19/19	1	NM_030913.6	P4	Q9H3T2-1
SEMA6C	ENST00000368913.7 linkuse as main transcript	c.2222T>C	p.Val741Ala	missense_variant	20/20	1		A1	Q9H3T2-3
SEMA6C	ENST00000341697.7 linkuse as main transcript	c.2126T>C	p.Val709Ala	missense_variant	19/19	1		P4	Q9H3T2-1
SEMA6C	ENST00000368912.7 linkuse as main transcript	c.2102T>C	p.Val701Ala	missense_variant	19/19	1			Q9H3T2-2

Frequencies

GnomAD3 genomes

AF:

0.0000199

AC:

AN:

150528

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000198

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000577

AC:

AN:

173352

Hom.:

AF XY:

0.0000307

AC XY:

AN XY:

97704

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000397

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000785

AC:

AN:

1401870

Hom.:

Cov.:

AF XY:

0.00000574

AC XY:

AN XY:

696434

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000305

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000199

AC:

AN:

150528

Hom.:

Cov.:

AF XY:

0.0000272

AC XY:

AN XY:

73498

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000198

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000302

ExAC

AF:

0.0000699

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 16, 2021

The c.2222T>C (p.V741A) alteration is located in exon 20 (coding exon 18) of the SEMA6C gene. This alteration results from a T to C substitution at nucleotide position 2222, causing the valine (V) at amino acid position 741 to be replaced by an alanine (A). 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

0.081

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.75

CADD

Benign

DANN

Benign

0.85

Eigen

Benign

-0.58

Eigen_PC

Benign

-0.49

FATHMM_MKL

Benign

0.23

LIST_S2

Benign

0.73

T;T;.;T

M_CAP

Benign

0.078

MetaRNN

Benign

0.026

T;T;T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

0.81

N;N;N;N

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

-0.14

N;N;N;N

REVEL

Benign

0.050

Sift

Benign

0.21

T;T;T;T

Sift4G

Benign

0.70

T;T;T;T

Polyphen

0.0

B;B;B;B

Vest4

0.039

MutPred

0.11

.;.;Loss of methylation at K710 (P = 0.0479);Loss of methylation at K710 (P = 0.0479);

MVP

0.29

MPC

0.73

ClinPred

0.043

GERP RS

1.4

Varity_R

0.033

gMVP

0.23

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