rs501916

Variant names:

• chr15-47761032-C-A
• rs501916
• NM_001358351.3:c.276C>A

Your query was ambiguous. Multiple possible variants found:

• chr15-47761032-C-A
• chr15-47761032-C-G
• chr15-47761032-C-T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001358351.3(SEMA6D):​c.276C>A​(p.Pro92Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.363 in 1,610,896 control chromosomes in the GnomAD database, including 111,192 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 0.41 (13723 hom., cov: 34)
  • Exomes 𝑓: 0.36 (97469 hom.)
• Consequence: SEMA6D NM_001358351.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.127
• Publications: 16 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP7: Synonymous conserved (PhyloP=0.127 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.616 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001358351.3. 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.276C>A	p.Pro92Pro	synonymous	Exon 4 of 19	NP_001345280.1
	SEMA6D	NM_001358352.2		c.276C>A	p.Pro92Pro	synonymous	Exon 4 of 19	NP_001345281.1
	SEMA6D	NM_153618.2		c.276C>A	p.Pro92Pro	synonymous	Exon 4 of 19	NP_705871.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEMA6D	ENST00000536845.7	TSL:2 MANE Select	c.276C>A	p.Pro92Pro	synonymous	Exon 4 of 19	ENSP00000446152.3
	SEMA6D	ENST00000316364.9	TSL:1	c.276C>A	p.Pro92Pro	synonymous	Exon 4 of 19	ENSP00000324857.5
	SEMA6D	ENST00000354744.8	TSL:1	c.276C>A	p.Pro92Pro	synonymous	Exon 4 of 18	ENSP00000346786.4

Frequencies

GnomAD3 genomes AF: 0.412 AC: 62596 AN: 151930 Hom.: 13705 Cov.: 34

Gnomad AFR AF: 0.537

Gnomad AMI AF: 0.427

Gnomad AMR AF: 0.403

Gnomad ASJ AF: 0.300

Gnomad EAS AF: 0.634

Gnomad SAS AF: 0.411

Gnomad FIN AF: 0.429

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.325

Gnomad OTH AF: 0.402

GnomAD2 exomes AF: 0.401 AC: 99965 AN: 249210 AF XY: 0.393

Gnomad AFR exome AF: 0.544

Gnomad AMR exome AF: 0.450

Gnomad ASJ exome AF: 0.295

Gnomad EAS exome AF: 0.647

Gnomad FIN exome AF: 0.429

Gnomad NFE exome AF: 0.330

Gnomad OTH exome AF: 0.378

GnomAD4 exome AF: 0.358 AC: 522381 AN: 1458848 Hom.: 97469 Cov.: 34 AF XY: 0.358 AC XY: 260167 AN XY: 725792

African (AFR) AF: 0.543 AC: 18110 AN: 33374

American (AMR) AF: 0.449 AC: 20021 AN: 44546

Ashkenazi Jewish (ASJ) AF: 0.295 AC: 7683 AN: 26080

East Asian (EAS) AF: 0.662 AC: 26183 AN: 39556

South Asian (SAS) AF: 0.403 AC: 34704 AN: 86106

European-Finnish (FIN) AF: 0.421 AC: 22462 AN: 53344

Middle Eastern (MID) AF: 0.312 AC: 1790 AN: 5744

European-Non Finnish (NFE) AF: 0.332 AC: 368960 AN: 1109824

Other (OTH) AF: 0.373 AC: 22468 AN: 60274

GnomAD4 genome AF: 0.412 AC: 62666 AN: 152048 Hom.: 13723 Cov.: 34 AF XY: 0.419 AC XY: 31134 AN XY: 74304

African (AFR) AF: 0.537 AC: 22268 AN: 41476

American (AMR) AF: 0.404 AC: 6167 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.300 AC: 1041 AN: 3470

East Asian (EAS) AF: 0.634 AC: 3277 AN: 5172

South Asian (SAS) AF: 0.410 AC: 1975 AN: 4818

European-Finnish (FIN) AF: 0.429 AC: 4526 AN: 10550

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.325 AC: 22085 AN: 67960

Other (OTH) AF: 0.403 AC: 852 AN: 2114

Alfa AF: 0.350 Hom.: 32915

Bravo AF: 0.421

Asia WGS AF: 0.526 AC: 1827 AN: 3478

EpiCase AF: 0.315

EpiControl AF: 0.322

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	2.4
DANN	Benign	0.57
PhyloP100		0.13
Mutation Taster		=97/3	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: rs501916; hg19: chr15-48053229; COSMIC: COSV108144110; COSMIC: COSV108144110;