rs1045688

Variant names:

• chr15-47773290-C-T
• rs1045688
• NM_001358351.3:c.*1505C>T

Variant summary

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

The NM_001358351.3(SEMA6D):​c.*1505C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.213 in 152,568 control chromosomes in the GnomAD database, including 4,005 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 0.21 (3980 hom., cov: 32)
  • Exomes 𝑓: 0.31 (25 hom.)
• Consequence: SEMA6D NM_001358351.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.20
• Publications: 3 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=-0.35).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.27 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEMA6D	NM_001358351.3	MANE Select	c.*1505C>T		3_prime_UTR	Exon 19 of 19	NP_001345280.1
	SEMA6D	NM_001358352.2		c.*1505C>T		3_prime_UTR	Exon 19 of 19	NP_001345281.1
	SEMA6D	NM_153618.2		c.*1505C>T		3_prime_UTR	Exon 19 of 19	NP_705871.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEMA6D	ENST00000536845.7	TSL:2 MANE Select	c.*1505C>T		3_prime_UTR	Exon 19 of 19	ENSP00000446152.3
	SEMA6D	ENST00000316364.9	TSL:1	c.*1505C>T		3_prime_UTR	Exon 19 of 19	ENSP00000324857.5
	SEMA6D	ENST00000354744.8	TSL:1	c.*1505C>T		3_prime_UTR	Exon 18 of 18	ENSP00000346786.4

Frequencies

GnomAD3 genomes AF: 0.213 AC: 32335 AN: 152016 Hom.: 3980 Cov.: 32

Gnomad AFR AF: 0.0870

Gnomad AMI AF: 0.304

Gnomad AMR AF: 0.213

Gnomad ASJ AF: 0.246

Gnomad EAS AF: 0.169

Gnomad SAS AF: 0.283

Gnomad FIN AF: 0.307

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.269

Gnomad OTH AF: 0.229

GnomAD4 exome AF: 0.313 AC: 136 AN: 434 Hom.: 25 Cov.: 0 AF XY: 0.313 AC XY: 82 AN XY: 262

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.312 AC: 133 AN: 426

Middle Eastern (MID) AF: 0.500 AC: 1 AN: 2

European-Non Finnish (NFE) AF: 0.500 AC: 1 AN: 2

Other (OTH) AF: 0.250 AC: 1 AN: 4

GnomAD4 genome AF: 0.213 AC: 32352 AN: 152134 Hom.: 3980 Cov.: 32 AF XY: 0.217 AC XY: 16155 AN XY: 74356

African (AFR) AF: 0.0871 AC: 3618 AN: 41530

American (AMR) AF: 0.213 AC: 3255 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.246 AC: 854 AN: 3468

East Asian (EAS) AF: 0.170 AC: 879 AN: 5174

South Asian (SAS) AF: 0.283 AC: 1362 AN: 4820

European-Finnish (FIN) AF: 0.307 AC: 3243 AN: 10576

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.269 AC: 18312 AN: 67988

Other (OTH) AF: 0.227 AC: 479 AN: 2110

Alfa AF: 0.244 Hom.: 6285

Bravo AF: 0.200

Asia WGS AF: 0.223 AC: 774 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	18
DANN	Benign	0.92
PhyloP100		3.2
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: rs1045688; hg19: chr15-48065487; COSMIC: COSV60383562; COSMIC: COSV60383562;