rs16960071

Variant names:

• chr15-47766572-T-A
• rs16960071
• NM_001358351.3:c.1647-44T>A

Your query was ambiguous. Multiple possible variants found:

• chr15-47766572-T-A
• chr15-47766572-T-C

Variant summary

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

The NM_001358352.2(SEMA6D):​c.1647-5T>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0315 in 1,600,272 control chromosomes in the GnomAD database, including 1,110 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as (no stars).

• Frequency:
  • Genomes: 𝑓 0.024 (88 hom., cov: 32)
  • Exomes 𝑓: 0.032 (1022 hom.)
• Consequence: SEMA6D NM_001358352.2 splice_region, intron
• Scores: Splicing: ADA: 0.009559
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.91
• Publications: 5 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=-0.43).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0729 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001358352.2. 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_001358351.3	MANE Select	c.1647-44T>A		intron	N/A	NP_001345280.1	Q8NFY4-1
	SEMA6D	NM_001358352.2		c.1647-5T>A		splice_region intron	N/A	NP_001345281.1
	SEMA6D	NM_153618.2		c.1647-44T>A		intron	N/A	NP_705871.1	Q8NFY4-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEMA6D	ENST00000536845.7	TSL:2 MANE Select	c.1647-44T>A		intron	N/A	ENSP00000446152.3	Q8NFY4-1
	SEMA6D	ENST00000316364.9	TSL:1	c.1647-44T>A		intron	N/A	ENSP00000324857.5	Q8NFY4-1
	SEMA6D	ENST00000354744.8	TSL:1	c.1647-44T>A		intron	N/A	ENSP00000346786.4	Q8NFY4-4

Frequencies

GnomAD3 genomes AF: 0.0238 AC: 3618 AN: 152088 Hom.: 89 Cov.: 32

Gnomad AFR AF: 0.00529

Gnomad AMI AF: 0.0515

Gnomad AMR AF: 0.0111

Gnomad ASJ AF: 0.00375

Gnomad EAS AF: 0.0577

Gnomad SAS AF: 0.0805

Gnomad FIN AF: 0.0422

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0293

Gnomad OTH AF: 0.0181

GnomAD2 exomes AF: 0.0332 AC: 8304 AN: 250224 AF XY: 0.0354

Gnomad AFR exome AF: 0.00550

Gnomad AMR exome AF: 0.00981

Gnomad ASJ exome AF: 0.00518

Gnomad EAS exome AF: 0.0682

Gnomad FIN exome AF: 0.0460

Gnomad NFE exome AF: 0.0279

Gnomad OTH exome AF: 0.0251

GnomAD4 exome AF: 0.0324 AC: 46866 AN: 1448066 Hom.: 1022 Cov.: 28 AF XY: 0.0335 AC XY: 24175 AN XY: 721374

African (AFR) AF: 0.00419 AC: 139 AN: 33156

American (AMR) AF: 0.0104 AC: 466 AN: 44638

Ashkenazi Jewish (ASJ) AF: 0.00478 AC: 124 AN: 25950

East Asian (EAS) AF: 0.0430 AC: 1697 AN: 39502

South Asian (SAS) AF: 0.0683 AC: 5856 AN: 85766

European-Finnish (FIN) AF: 0.0449 AC: 2389 AN: 53216

Middle Eastern (MID) AF: 0.00384 AC: 22 AN: 5730

European-Non Finnish (NFE) AF: 0.0311 AC: 34262 AN: 1100262

Other (OTH) AF: 0.0319 AC: 1911 AN: 59846

GnomAD4 genome AF: 0.0237 AC: 3613 AN: 152206 Hom.: 88 Cov.: 32 AF XY: 0.0259 AC XY: 1927 AN XY: 74426

African (AFR) AF: 0.00527 AC: 219 AN: 41548

American (AMR) AF: 0.0111 AC: 169 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00375 AC: 13 AN: 3470

East Asian (EAS) AF: 0.0578 AC: 299 AN: 5170

South Asian (SAS) AF: 0.0795 AC: 383 AN: 4818

European-Finnish (FIN) AF: 0.0422 AC: 448 AN: 10608

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0293 AC: 1994 AN: 67998

Other (OTH) AF: 0.0184 AC: 39 AN: 2116

Alfa AF: 0.0173 Hom.: 15

Bravo AF: 0.0197

Asia WGS AF: 0.0790 AC: 274 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Pathogenic	31
DANN	Benign	0.88
PhyloP100		1.9
PromoterAI		0.0023	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0096
dbscSNV1_RF	Benign	0.024
SpliceAI score (max)		0.51		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.51		Position offset: 2

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

Other links and lift over

dbSNP: rs16960071; hg19: chr15-48058769;