Variant rs501916 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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

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 -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/exons	MANE	Protein	UniProt
SEMA6D	NM_001358351.3 linkuse as main transcript	c.276C>A	p.Pro92Pro	synonymous_variant	4/19	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.276C>A	p.Pro92Pro	synonymous_variant	4/19	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

GnomAD3 exomes

AF:

0.401

AC:

99965

AN:

249210

Hom.:

21411

AF XY:

0.393

AC XY:

52969

AN XY:

134702

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 SAS exome

AF:

0.408

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

Gnomad4 AFR exome

AF:

0.543

Gnomad4 AMR exome

AF:

0.449

Gnomad4 ASJ exome

AF:

0.295

Gnomad4 EAS exome

AF:

0.662

Gnomad4 SAS exome

AF:

0.403

Gnomad4 FIN exome

AF:

0.421

Gnomad4 NFE exome

AF:

0.332

Gnomad4 OTH exome

AF:

0.373

GnomAD4 genome

AF:

0.412

AC:

62666

AN:

152048

Hom.:

13723

Cov.:

AF XY:

0.419

AC XY:

31134

AN XY:

74304

show subpopulations

Gnomad4 AFR

AF:

0.537

Gnomad4 AMR

AF:

0.404

Gnomad4 ASJ

AF:

0.300

Gnomad4 EAS

AF:

0.634

Gnomad4 SAS

AF:

0.410

Gnomad4 FIN

AF:

0.429

Gnomad4 NFE

AF:

0.325

Gnomad4 OTH

AF:

0.403

Alfa

AF:

0.340

Hom.:

21366

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

DANN

Benign

0.57

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

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