Variant rs3743281 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP7BA1

The NM_001358351.3(SEMA6D):c.1221C>T(p.Ala407=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 1,613,698 control chromosomes in the GnomAD database, including 53,344 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 0.20 ( 3650 hom., cov: 33)

Exomes 𝑓: 0.26 ( 49694 hom. )

Consequence

SEMA6D
NM_001358351.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.17

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.28).

BP7

Synonymous conserved (PhyloP=-1.17 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.297 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEMA6D	NM_001358351.3 linkuse as main transcript	c.1221C>T	p.Ala407=	synonymous_variant	12/19	ENST00000536845.7	NP_001345280.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEMA6D	ENST00000536845.7 linkuse as main transcript	c.1221C>T	p.Ala407=	synonymous_variant	12/19	2	NM_001358351.3	ENSP00000446152	P4	Q8NFY4-1

Frequencies

GnomAD3 genomes

AF:

0.201

AC:

30584

AN:

152048

Hom.:

3649

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0683

Gnomad AMI

AF:

0.279

Gnomad AMR

AF:

0.200

Gnomad ASJ

AF:

0.223

Gnomad EAS

AF:

0.186

Gnomad SAS

AF:

0.312

Gnomad FIN

AF:

0.319

Gnomad MID

AF:

0.161

Gnomad NFE

AF:

0.255

Gnomad OTH

AF:

0.207

GnomAD3 exomes

AF:

0.244

AC:

61143

AN:

251024

Hom.:

8041

AF XY:

0.252

AC XY:

34131

AN XY:

135632

show subpopulations

Gnomad AFR exome

AF:

0.0673

Gnomad AMR exome

AF:

0.192

Gnomad ASJ exome

AF:

0.220

Gnomad EAS exome

AF:

0.191

Gnomad SAS exome

AF:

0.310

Gnomad FIN exome

AF:

0.327

Gnomad NFE exome

AF:

0.261

Gnomad OTH exome

AF:

0.247

GnomAD4 exome

AF:

0.257

AC:

375103

AN:

1461532

Hom.:

49694

Cov.:

AF XY:

0.259

AC XY:

188539

AN XY:

727068

show subpopulations

Gnomad4 AFR exome

AF:

0.0612

Gnomad4 AMR exome

AF:

0.194

Gnomad4 ASJ exome

AF:

0.218

Gnomad4 EAS exome

AF:

0.208

Gnomad4 SAS exome

AF:

0.307

Gnomad4 FIN exome

AF:

0.320

Gnomad4 NFE exome

AF:

0.262

Gnomad4 OTH exome

AF:

0.243

GnomAD4 genome

AF:

0.201

AC:

30597

AN:

152166

Hom.:

3650

Cov.:

AF XY:

0.207

AC XY:

15372

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.0683

Gnomad4 AMR

AF:

0.201

Gnomad4 ASJ

AF:

0.223

Gnomad4 EAS

AF:

0.187

Gnomad4 SAS

AF:

0.311

Gnomad4 FIN

AF:

0.319

Gnomad4 NFE

AF:

0.255

Gnomad4 OTH

AF:

0.205

Alfa

AF:

0.238

Hom.:

7284

Bravo

AF:

0.185

Asia WGS

AF:

0.232

AC:

806

AN:

3478

EpiCase

AF:

0.247

EpiControl

AF:

0.250

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.28

CADD

Benign

1.3

DANN

Benign

0.82

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over