rs1045688

chr15-47773290-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001358351.3(SEMA6D):c.*1505C>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 0.213 in 152,568 control chromosomes in the GnomAD database, including 4,005 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 0.21 (3980 hom., cov: 32)
  • Exomes 𝑓: 0.31 (25 hom.)
• Consequence: SEMA6D NM_001358351.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.20

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.27 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SEMA6D	NM_001358351.3	c.*1505C>T		3_prime_UTR_variant	19/19	ENST00000536845.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEMA6D	ENST00000536845.7	c.*1505C>T		3_prime_UTR_variant	19/19	2	NM_001358351.3	P4

Frequencies

GnomAD3 genomes AF: 0.213 AC: 32335 AN: 152016 Hom.: 3980 Cov.: 32

Gnomad AFR AF: 0.0870

Gnomad AMI AF: 0.304

Gnomad AMR AF: 0.213

Gnomad ASJ AF: 0.246

Gnomad EAS AF: 0.169

Gnomad SAS AF: 0.283

Gnomad FIN AF: 0.307

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.269

Gnomad OTH AF: 0.229

GnomAD4 exome AF: 0.313 AC: 136 AN: 434 Hom.: 25 Cov.: 0 AF XY: 0.313 AC XY: 82 AN XY: 262

Gnomad4 FIN exome AF: 0.312

Gnomad4 NFE exome AF: 0.500

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.213 AC: 32352 AN: 152134 Hom.: 3980 Cov.: 32 AF XY: 0.217 AC XY: 16155 AN XY: 74356

Gnomad4 AFR AF: 0.0871

Gnomad4 AMR AF: 0.213

Gnomad4 ASJ AF: 0.246

Gnomad4 EAS AF: 0.170

Gnomad4 SAS AF: 0.283

Gnomad4 FIN AF: 0.307

Gnomad4 NFE AF: 0.269

Gnomad4 OTH AF: 0.227

Alfa AF: 0.251 Hom.: 5012

Bravo AF: 0.200

Asia WGS AF: 0.223 AC: 774 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
Cadd	Benign	18
Dann	Benign	0.92

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1045688; hg19: chr15-48065487; COSMIC: COSV60383562; COSMIC: COSV60383562;