Variant 1-151138034-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_030913.6(SEMA6C):c.619C>T(p.Pro207Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00592 in 1,614,248 control chromosomes in the GnomAD database, including 44 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0045 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0061 ( 41 hom. )

Consequence

SEMA6C
NM_030913.6 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.13

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 Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0053745806).

BP6

Variant 1-151138034-G-A is Benign according to our data. Variant chr1-151138034-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2639168.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEMA6C	NM_030913.6 link	c.619C>T	p.Pro207Ser	missense_variant	9/19	ENST00000368914.8	NP_112175.2	Q9H3T2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEMA6C	ENST00000368914.8 link	c.619C>T	p.Pro207Ser	missense_variant	9/19	1	NM_030913.6	ENSP00000357910.3		Q9H3T2-1

Frequencies

GnomAD3 genomes

AF:

0.00449

AC:

684

AN:

152252

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00128

Gnomad AMI

AF:

0.0351

Gnomad AMR

AF:

0.00150

Gnomad ASJ

AF:

0.00259

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00248

Gnomad FIN

AF:

0.00376

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00741

Gnomad OTH

AF:

0.00383

GnomAD3 exomes

AF:

0.00411

AC:

1031

AN:

251122

Hom.:

AF XY:

0.00424

AC XY:

576

AN XY:

135748

show subpopulations

Gnomad AFR exome

AF:

0.000862

Gnomad AMR exome

AF:

0.000868

Gnomad ASJ exome

AF:

0.00199

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00212

Gnomad FIN exome

AF:

0.00324

Gnomad NFE exome

AF:

0.00707

Gnomad OTH exome

AF:

0.00489

GnomAD4 exome

AF:

0.00607

AC:

8874

AN:

1461878

Hom.:

Cov.:

AF XY:

0.00598

AC XY:

4350

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.000627

Gnomad4 AMR exome

AF:

0.000850

Gnomad4 ASJ exome

AF:

0.00256

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00220

Gnomad4 FIN exome

AF:

0.00318

Gnomad4 NFE exome

AF:

0.00724

Gnomad4 OTH exome

AF:

0.00535

GnomAD4 genome

AF:

0.00449

AC:

684

AN:

152370

Hom.:

Cov.:

AF XY:

0.00421

AC XY:

314

AN XY:

74516

show subpopulations

Gnomad4 AFR

AF:

0.00127

Gnomad4 AMR

AF:

0.00150

Gnomad4 ASJ

AF:

0.00259

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00248

Gnomad4 FIN

AF:

0.00376

Gnomad4 NFE

AF:

0.00741

Gnomad4 OTH

AF:

0.00379

Alfa

AF:

0.00621

Hom.:

Bravo

AF:

0.00424

TwinsUK

AF:

0.00405

AC:

ALSPAC

AF:

0.00986

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00756

AC:

ExAC

AF:

0.00451

AC:

547

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.00534

EpiControl

AF:

0.00569

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Dec 01, 2022

SEMA6C: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.71

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.024

.;T;T;T;T

Eigen

Benign

-0.67

Eigen_PC

Benign

-0.52

FATHMM_MKL

Benign

0.66

LIST_S2

Benign

0.84

T;.;T;T;T

M_CAP

Benign

0.0055

MetaRNN

Benign

0.0054

T;T;T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

-0.43

N;N;N;.;.

PrimateAI

Benign

0.39

PROVEAN

Benign

-0.73

N;N;N;.;.

REVEL

Benign

0.041

Sift

Benign

0.052

T;T;T;.;.

Sift4G

Uncertain

0.016

D;D;D;T;T

Polyphen

0.0010

B;B;B;.;.

Vest4

0.17

MVP

0.37

MPC

1.1

ClinPred

0.018

GERP RS

1.9

Varity_R

0.054

gMVP

0.30

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