15-47765422-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000389425.7(SEMA6D):c.*362C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.6 in 1,024,508 control chromosomes in the GnomAD database, including 185,791 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 0.64 (31210 hom., cov: 30)
  • Exomes 𝑓: 0.59 (154581 hom.)
• Consequence: SEMA6D ENST00000389425.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.698

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.74 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SEMA6D	NM_001358351.3	c.1427+366C>T		intron_variant		ENST00000536845.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEMA6D	ENST00000536845.7	c.1427+366C>T		intron_variant		2	NM_001358351.3	P4

Frequencies

GnomAD3 genomes AF: 0.639 AC: 96745 AN: 151496 Hom.: 31183 Cov.: 30

Gnomad AFR AF: 0.667

Gnomad AMI AF: 0.524

Gnomad AMR AF: 0.645

Gnomad ASJ AF: 0.604

Gnomad EAS AF: 0.760

Gnomad SAS AF: 0.626

Gnomad FIN AF: 0.721

Gnomad MID AF: 0.582

Gnomad NFE AF: 0.602

Gnomad OTH AF: 0.640

GnomAD4 exome AF: 0.593 AC: 517968 AN: 872896 Hom.: 154581 Cov.: 23 AF XY: 0.595 AC XY: 241106 AN XY: 405344

Gnomad4 AFR exome AF: 0.666

Gnomad4 AMR exome AF: 0.660

Gnomad4 ASJ exome AF: 0.592

Gnomad4 EAS exome AF: 0.756

Gnomad4 SAS exome AF: 0.613

Gnomad4 FIN exome AF: 0.688

Gnomad4 NFE exome AF: 0.589

Gnomad4 OTH exome AF: 0.612

GnomAD4 genome AF: 0.639 AC: 96814 AN: 151612 Hom.: 31210 Cov.: 30 AF XY: 0.647 AC XY: 47910 AN XY: 74056

Gnomad4 AFR AF: 0.666

Gnomad4 AMR AF: 0.646

Gnomad4 ASJ AF: 0.604

Gnomad4 EAS AF: 0.760

Gnomad4 SAS AF: 0.626

Gnomad4 FIN AF: 0.721

Gnomad4 NFE AF: 0.602

Gnomad4 OTH AF: 0.639

Alfa AF: 0.601 Hom.: 20678

Bravo AF: 0.634

Asia WGS AF: 0.691 AC: 2402 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.86
Dann	Benign	0.25

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: rs537052; hg19: chr15-48057619;