rs16959955

Variant names:

• chr15-47710503-T-C
• rs16959955
• ENST00000558014.5:c.-54-49242T>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000558014.5(SEMA6D):​c.-54-49242T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 152,106 control chromosomes in the GnomAD database, including 3,392 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 0.19 (3392 hom., cov: 31)
• Consequence: SEMA6D ENST00000558014.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.561
• Publications: 1 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.28).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.247 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEMA6D	NM_001198999.2	c.-54-49242T>C		intron_variant	Intron 4 of 19		NP_001185928.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEMA6D	ENST00000558014.5	c.-54-49242T>C		intron_variant	Intron 4 of 19	1		ENSP00000452815.1
SEMA6D	ENST00000559184.5	c.-54-49242T>C		intron_variant	Intron 5 of 5	4		ENSP00000453097.1
SEMA6D	ENST00000560636.5	c.-54-49242T>C		intron_variant	Intron 5 of 5	4		ENSP00000453420.1

Frequencies

GnomAD3 genomes AF: 0.191 AC: 29000 AN: 151988 Hom.: 3394 Cov.: 31

Gnomad AFR AF: 0.0947

Gnomad AMI AF: 0.135

Gnomad AMR AF: 0.172

Gnomad ASJ AF: 0.270

Gnomad EAS AF: 0.00481

Gnomad SAS AF: 0.164

Gnomad FIN AF: 0.295

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.250

Gnomad OTH AF: 0.198

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

GnomAD4 genome AF: 0.191 AC: 28997 AN: 152106 Hom.: 3392 Cov.: 31 AF XY: 0.193 AC XY: 14320 AN XY: 74338

African (AFR) AF: 0.0947 AC: 3933 AN: 41532

American (AMR) AF: 0.171 AC: 2620 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.270 AC: 936 AN: 3466

East Asian (EAS) AF: 0.00482 AC: 25 AN: 5184

South Asian (SAS) AF: 0.164 AC: 792 AN: 4828

European-Finnish (FIN) AF: 0.295 AC: 3095 AN: 10508

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.250 AC: 16992 AN: 67982

Other (OTH) AF: 0.196 AC: 414 AN: 2116

Alfa AF: 0.233 Hom.: 2621

Bravo AF: 0.172

Asia WGS AF: 0.0920 AC: 321 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.28
CADD	Benign	15
DANN	Benign	0.70
PhyloP100		0.56
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs16959955; hg19: chr15-48002700;