rs3743279

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_001358351.3(SEMA6D):c.920A>G(p.Asn307Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0195 in 1,613,834 control chromosomes in the GnomAD database, including 2,915 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.074 ( 1250 hom., cov: 33)

Exomes 𝑓: 0.014 ( 1665 hom. )

Consequence

SEMA6D
NM_001358351.3 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 4.54

Publications

11 publications found

Variant links:

Genes affected

SEMA6D (HGNC:16770): (semaphorin 6D) Semaphorins are a large family, including both secreted and membrane associated proteins, many of which have been implicated as inhibitors or chemorepellents in axon pathfinding, fasciculation and branching, and target selection. All semaphorins possess a semaphorin (Sema) domain and a PSI domain (found in plexins, semaphorins and integrins) in the N-terminal extracellular portion. Additional sequence motifs C-terminal to the semaphorin domain allow classification into distinct subfamilies. Results demonstrate that transmembrane semaphorins, like the secreted ones, can act as repulsive axon guidance cues. This gene encodes a class 6 vertebrate transmembrane semaphorin that demonstrates alternative splicing. Several transcript variants have been identified and expression of the distinct encoded isoforms is thought to be regulated in a tissue- and development-dependent manner. [provided by RefSeq, Nov 2010]

SEMA6D Gene-Disease associations (from GenCC):

complex neurodevelopmental disorder
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

SEMA6D links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0015435815).

BP6

Variant 15-47764022-A-G is Benign according to our data. Variant chr15-47764022-A-G is described in ClinVar as Benign. ClinVar VariationId is 3057033.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.234 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEMA6D	NM_001358351.3 link	c.920A>G	p.Asn307Ser	missense_variant	Exon 10 of 19	ENST00000536845.7	NP_001345280.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEMA6D	ENST00000536845.7 link	c.920A>G	p.Asn307Ser	missense_variant	Exon 10 of 19	2	NM_001358351.3	ENSP00000446152.3		Q8NFY4-1

Frequencies

GnomAD3 genomes

AF:

0.0735

AC:

11177

AN:

152060

Hom.:

1241

Cov.:

show subpopulations

Gnomad AFR

AF:

0.238

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0216

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0714

Gnomad SAS

AF:

0.106

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000544

Gnomad OTH

AF:

0.0440

GnomAD2 exomes

AF:

0.0343

AC:

8590

AN:

250584

AF XY:

0.0330

show subpopulations

Gnomad AFR exome

AF:

0.244

Gnomad AMR exome

AF:

0.00859

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0707

Gnomad FIN exome

AF:

0.0000924

Gnomad NFE exome

AF:

0.000611

Gnomad OTH exome

AF:

0.0149

GnomAD4 exome

AF:

0.0139

AC:

20276

AN:

1461656

Hom.:

1665

Cov.:

AF XY:

0.0150

AC XY:

10935

AN XY:

727136

show subpopulations

African (AFR)

AF:

0.248

AC:

8291

AN:

33458

American (AMR)

AF:

0.0103

AC:

459

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26126

East Asian (EAS)

AF:

0.0519

AC:

2061

AN:

39680

South Asian (SAS)

AF:

0.0868

AC:

7484

AN:

86252

European-Finnish (FIN)

AF:

0.0000374

AC:

AN:

53414

Middle Eastern (MID)

AF:

0.0106

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.000288

AC:

320

AN:

1111858

Other (OTH)

AF:

0.0265

AC:

1598

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

1120

2240

3361

4481

5601

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

386

772

1158

1544

1930

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0738

AC:

11232

AN:

152178

Hom.:

1250

Cov.:

AF XY:

0.0725

AC XY:

5394

AN XY:

74376

show subpopulations

African (AFR)

AF:

0.238

AC:

9888

AN:

41490

American (AMR)

AF:

0.0215

AC:

329

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.0716

AC:

369

AN:

5156

South Asian (SAS)

AF:

0.105

AC:

504

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000544

AC:

AN:

68012

Other (OTH)

AF:

0.0482

AC:

102

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

439

878

1318

1757

2196

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

116

232

348

464

580

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0211

Hom.:

952

Bravo

AF:

0.0799

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.227

AC:

999

ESP6500EA

AF:

0.000582

AC:

ExAC

AF:

0.0396

AC:

4809

Asia WGS

AF:

0.114

AC:

396

AN:

3476

EpiCase

AF:

0.000763

EpiControl

AF:

0.000830

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

SEMA6D-related disorder

Benign:1

Jan 14, 2020

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.76

BayesDel_noAF

Benign

-0.73

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.19

.;T;.;.;.;T;.;.;.

Eigen

Benign

-0.23

Eigen_PC

Benign

-0.18

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.79

.;.;.;T;T;T;T;T;T

MetaRNN

Benign

0.0015

T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

1.1

L;L;L;L;L;L;L;L;L

PhyloP100

4.5

PrimateAI

Uncertain

0.53

PROVEAN

Uncertain

-3.2

D;D;D;D;D;D;D;D;D

REVEL

Benign

0.14

Sift

Benign

0.073

T;T;T;T;T;T;T;T;T

Sift4G

Benign

0.066

T;T;T;T;T;T;T;T;T

Polyphen

0.98

D;B;.;.;.;B;D;D;D

Vest4

0.13

MPC

0.52

ClinPred

0.067

GERP RS

1.1

Varity_R

0.33

gMVP

0.12

Mutation Taster

=92/8

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over