rs955845

Variant names:

• chr15-47696962-A-G
• rs955845
• ENST00000558014.5:c.-54-62783A>G

Variant summary

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

The NM_001198999.2(SEMA6D):​c.-54-62783A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.298 in 152,118 control chromosomes in the GnomAD database, including 8,457 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 0.30 (8457 hom., cov: 32)
• Consequence: SEMA6D NM_001198999.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.849
• 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=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.408 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001198999.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEMA6D	NM_001198999.2		c.-54-62783A>G		intron	N/A	NP_001185928.1	Q8NFY4-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEMA6D	ENST00000558014.5	TSL:1	c.-54-62783A>G		intron	N/A	ENSP00000452815.1	Q8NFY4-2
	SEMA6D	ENST00000559184.5	TSL:4	c.-54-62783A>G		intron	N/A	ENSP00000453097.1	H0YL82
	SEMA6D	ENST00000560636.5	TSL:4	c.-54-62783A>G		intron	N/A	ENSP00000453420.1

Frequencies

GnomAD3 genomes AF: 0.298 AC: 45317 AN: 152000 Hom.: 8454 Cov.: 32

Gnomad AFR AF: 0.0810

Gnomad AMI AF: 0.370

Gnomad AMR AF: 0.343

Gnomad ASJ AF: 0.409

Gnomad EAS AF: 0.232

Gnomad SAS AF: 0.272

Gnomad FIN AF: 0.345

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.412

Gnomad OTH AF: 0.332

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

GnomAD4 genome AF: 0.298 AC: 45317 AN: 152118 Hom.: 8457 Cov.: 32 AF XY: 0.294 AC XY: 21877 AN XY: 74366

African (AFR) AF: 0.0808 AC: 3356 AN: 41552

American (AMR) AF: 0.343 AC: 5236 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.409 AC: 1420 AN: 3472

East Asian (EAS) AF: 0.232 AC: 1197 AN: 5166

South Asian (SAS) AF: 0.274 AC: 1318 AN: 4814

European-Finnish (FIN) AF: 0.345 AC: 3643 AN: 10570

Middle Eastern (MID) AF: 0.449 AC: 132 AN: 294

European-Non Finnish (NFE) AF: 0.412 AC: 27988 AN: 67976

Other (OTH) AF: 0.328 AC: 692 AN: 2110

Alfa AF: 0.313 Hom.: 1640

Bravo AF: 0.292

Asia WGS AF: 0.243 AC: 844 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.47
DANN	Benign	0.81
PhyloP100		-0.85
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs955845;

hg19: chr15-47989159;