dbSNP rs501916: SEMA6D:p.Pro92Pro (chr15-47761032-C-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_001358351.3(SEMA6D):c.276C>A(p.Pro92Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.363 in 1,610,896 control chromosomes in the GnomAD database, including 111,192 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.41 ( 13723 hom., cov: 34)

Exomes 𝑓: 0.36 ( 97469 hom. )

Consequence

SEMA6D
NM_001358351.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.127

Publications

16 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 (BayesDel_noAF=-0.54).

BP7

Synonymous conserved (PhyloP=0.127 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.616 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEMA6D	NM_001358351.3 link	c.276C>A	p.Pro92Pro	synonymous_variant	Exon 4 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.276C>A	p.Pro92Pro	synonymous_variant	Exon 4 of 19	2	NM_001358351.3	ENSP00000446152.3		Q8NFY4-1

Frequencies

GnomAD3 genomes

AF:

0.412

AC:

62596

AN:

151930

Hom.:

13705

Cov.:

show subpopulations

Gnomad AFR

AF:

0.537

Gnomad AMI

AF:

0.427

Gnomad AMR

AF:

0.403

Gnomad ASJ

AF:

0.300

Gnomad EAS

AF:

0.634

Gnomad SAS

AF:

0.411

Gnomad FIN

AF:

0.429

Gnomad MID

AF:

0.288

Gnomad NFE

AF:

0.325

Gnomad OTH

AF:

0.402

GnomAD2 exomes

AF:

0.401

AC:

99965

AN:

249210

AF XY:

0.393

show subpopulations

Gnomad AFR exome

AF:

0.544

Gnomad AMR exome

AF:

0.450

Gnomad ASJ exome

AF:

0.295

Gnomad EAS exome

AF:

0.647

Gnomad FIN exome

AF:

0.429

Gnomad NFE exome

AF:

0.330

Gnomad OTH exome

AF:

0.378

GnomAD4 exome

AF:

0.358

AC:

522381

AN:

1458848

Hom.:

97469

Cov.:

AF XY:

0.358

AC XY:

260167

AN XY:

725792

show subpopulations

African (AFR)

AF:

0.543

AC:

18110

AN:

33374

American (AMR)

AF:

0.449

AC:

20021

AN:

44546

Ashkenazi Jewish (ASJ)

AF:

0.295

AC:

7683

AN:

26080

East Asian (EAS)

AF:

0.662

AC:

26183

AN:

39556

South Asian (SAS)

AF:

0.403

AC:

34704

AN:

86106

European-Finnish (FIN)

AF:

0.421

AC:

22462

AN:

53344

Middle Eastern (MID)

AF:

0.312

AC:

1790

AN:

5744

European-Non Finnish (NFE)

AF:

0.332

AC:

368960

AN:

1109824

Other (OTH)

AF:

0.373

AC:

22468

AN:

60274

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.449

Heterozygous variant carriers

16690

33380

50071

66761

83451

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12366

24732

37098

49464

61830

<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:

0.412

AC:

62666

AN:

152048

Hom.:

13723

Cov.:

AF XY:

0.419

AC XY:

31134

AN XY:

74304

show subpopulations

African (AFR)

AF:

0.537

AC:

22268

AN:

41476

American (AMR)

AF:

0.404

AC:

6167

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.300

AC:

1041

AN:

3470

East Asian (EAS)

AF:

0.634

AC:

3277

AN:

5172

South Asian (SAS)

AF:

0.410

AC:

1975

AN:

4818

European-Finnish (FIN)

AF:

0.429

AC:

4526

AN:

10550

Middle Eastern (MID)

AF:

0.293

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.325

AC:

22085

AN:

67960

Other (OTH)

AF:

0.403

AC:

852

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1874

3748

5622

7496

9370

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

592

1184

1776

2368

2960

<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:

0.350

Hom.:

32915

Bravo

AF:

0.421

Asia WGS

AF:

0.526

AC:

1827

AN:

3478

EpiCase

AF:

0.315

EpiControl

AF:

0.322

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

2.4

(source)

DANN

Benign

0.57

PhyloP100

0.13

Mutation Taster

=97/3

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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

Computational scores

Splicing

Publications

Other links and lift over