rs17388803

Variant names:

• chr15-47735007-A-C
• rs17388803
• NM_001358351.3:c.-55+17315A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001358351.3(SEMA6D):​c.-55+17315A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0852 in 152,162 control chromosomes in the GnomAD database, including 748 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 0.085 (748 hom., cov: 32)
• Consequence: SEMA6D NM_001358351.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.138
• Publications: 2 publications found

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 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.117 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEMA6D	NM_001358351.3	c.-55+17315A>C		intron_variant	Intron 1 of 18	ENST00000536845.7	NP_001345280.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEMA6D	ENST00000536845.7	c.-55+17315A>C		intron_variant	Intron 1 of 18	2	NM_001358351.3	ENSP00000446152.3

Frequencies

GnomAD3 genomes AF: 0.0853 AC: 12965 AN: 152044 Hom.: 750 Cov.: 32

Gnomad AFR AF: 0.0218

Gnomad AMI AF: 0.0581

Gnomad AMR AF: 0.111

Gnomad ASJ AF: 0.216

Gnomad EAS AF: 0.00405

Gnomad SAS AF: 0.0994

Gnomad FIN AF: 0.0637

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.119

Gnomad OTH AF: 0.120

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0852 AC: 12958 AN: 152162 Hom.: 748 Cov.: 32 AF XY: 0.0838 AC XY: 6234 AN XY: 74378

African (AFR) AF: 0.0217 AC: 903 AN: 41526

American (AMR) AF: 0.111 AC: 1689 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.216 AC: 750 AN: 3470

East Asian (EAS) AF: 0.00406 AC: 21 AN: 5178

South Asian (SAS) AF: 0.0990 AC: 477 AN: 4816

European-Finnish (FIN) AF: 0.0637 AC: 675 AN: 10590

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.119 AC: 8089 AN: 67988

Other (OTH) AF: 0.119 AC: 251 AN: 2114

Alfa AF: 0.0961 Hom.: 666

Bravo AF: 0.0829

Asia WGS AF: 0.0520 AC: 180 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	4.4
DANN	Benign	0.82
PhyloP100		-0.14
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17388803; hg19: chr15-48027204;