15-47770879-T-C

Position:

• chr15-47770879-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001358351.3(SEMA6D):​c.2316T>C​(p.Pro772=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.651 in 1,613,666 control chromosomes in the GnomAD database, including 347,312 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 0.73 (42152 hom., cov: 31)
  • Exomes 𝑓: 0.64 (305160 hom.)
• Consequence: SEMA6D NM_001358351.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.752

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]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP7: Synonymous conserved (PhyloP=-0.752 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.92 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SEMA6D	NM_001358351.3	c.2316T>C	p.Pro772=	synonymous_variant	19/19	ENST00000536845.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEMA6D	ENST00000536845.7	c.2316T>C	p.Pro772=	synonymous_variant	19/19	2	NM_001358351.3	P4

Frequencies

GnomAD3 genomes AF: 0.732 AC: 111066 AN: 151828 Hom.: 42077 Cov.: 31

Gnomad AFR AF: 0.928

Gnomad AMI AF: 0.523

Gnomad AMR AF: 0.683

Gnomad ASJ AF: 0.645

Gnomad EAS AF: 0.832

Gnomad SAS AF: 0.728

Gnomad FIN AF: 0.752

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.621

Gnomad OTH AF: 0.702

GnomAD3 exomes AF: 0.694 AC: 173101 AN: 249470 Hom.: 61229 AF XY: 0.687 AC XY: 92859 AN XY: 135130

Gnomad AFR exome AF: 0.937

Gnomad AMR exome AF: 0.712

Gnomad ASJ exome AF: 0.643

Gnomad EAS exome AF: 0.836

Gnomad SAS exome AF: 0.721

Gnomad FIN exome AF: 0.745

Gnomad NFE exome AF: 0.620

Gnomad OTH exome AF: 0.667

GnomAD4 exome AF: 0.642 AC: 938517 AN: 1461720 Hom.: 305160 Cov.: 72 AF XY: 0.644 AC XY: 468422 AN XY: 727148

Gnomad4 AFR exome AF: 0.940

Gnomad4 AMR exome AF: 0.710

Gnomad4 ASJ exome AF: 0.640

Gnomad4 EAS exome AF: 0.838

Gnomad4 SAS exome AF: 0.712

Gnomad4 FIN exome AF: 0.741

Gnomad4 NFE exome AF: 0.612

Gnomad4 OTH exome AF: 0.666

GnomAD4 genome AF: 0.732 AC: 111201 AN: 151946 Hom.: 42152 Cov.: 31 AF XY: 0.740 AC XY: 54923 AN XY: 74254

Gnomad4 AFR AF: 0.928

Gnomad4 AMR AF: 0.684

Gnomad4 ASJ AF: 0.645

Gnomad4 EAS AF: 0.831

Gnomad4 SAS AF: 0.727

Gnomad4 FIN AF: 0.752

Gnomad4 NFE AF: 0.621

Gnomad4 OTH AF: 0.708

Alfa AF: 0.640 Hom.: 51316

Bravo AF: 0.734

Asia WGS AF: 0.804 AC: 2796 AN: 3478

EpiCase AF: 0.614

EpiControl AF: 0.609

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.7
DANN	Benign	0.52

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

Other links and lift over

dbSNP: rs568215; hg19: chr15-48063076;