Variant 1-151132845-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.2432C>T(p.Pro811Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000382 in 1,283,022 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000037 ( 0 hom. )

Consequence

SEMA6C
NM_030913.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.101

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:

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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=0.08074176).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SEMA6C	NM_030913.6 linkuse as main transcript	c.2432C>T	p.Pro811Leu	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.2432C>T	p.Pro811Leu	missense_variant	19/19	1	NM_030913.6	P4	Q9H3T2-1

Frequencies

GnomAD3 genomes

AF:

0.0000465

AC:

AN:

150580

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00174

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000148

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000371

AC:

AN:

1132442

Hom.:

Cov.:

AF XY:

0.0000475

AC XY:

AN XY:

547202

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000135

Gnomad4 ASJ exome

AF:

0.00249

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000422

Gnomad4 OTH exome

AF:

0.0000671

GnomAD4 genome

AF:

0.0000465

AC:

AN:

150580

Hom.:

Cov.:

AF XY:

0.0000408

AC XY:

AN XY:

73522

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00174

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000148

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000356

Hom.:

Bravo

AF:

0.0000567

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

Oct 18, 2021

The c.2528C>T (p.P843L) 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 2528, causing the proline (P) at amino acid position 843 to be replaced by a leucine (L). 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

0.079

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Uncertain

0.98

Eigen

Benign

-0.26

Eigen_PC

Benign

-0.29

FATHMM_MKL

Benign

0.70

LIST_S2

Benign

0.81

T;T;.;T

M_CAP

Uncertain

0.14

MetaRNN

Benign

0.081

T;T;T;T

MetaSVM

Benign

-0.89

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-1.2

N;N;N;N

REVEL

Benign

0.18

Sift

Uncertain

0.0010

D;D;D;D

Sift4G

Benign

0.17

T;T;T;T

Polyphen

0.18

B;D;B;B

Vest4

0.11

MutPred

0.22

.;.;Loss of glycosylation at P811 (P = 0.0664);Loss of glycosylation at P811 (P = 0.0664);

MVP

0.65

MPC

0.43

ClinPred

0.45

GERP RS

3.3

Varity_R

0.070

gMVP

0.55

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