15-47765422-C-T

Variant names:

• chr15-47765422-C-T
• rs537052
• ENST00000389425.7:c.*362C>T

Variant summary

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

The NM_024966.3(SEMA6D):​c.*362C>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 0.6 in 1,024,508 control chromosomes in the GnomAD database, including 185,791 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 0.64 (31210 hom., cov: 30)
  • Exomes 𝑓: 0.59 (154581 hom.)
• Consequence: SEMA6D NM_024966.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.698
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.74 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024966.3. 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.1427+366C>T		intron	N/A	NP_001345280.1	Q8NFY4-1
	SEMA6D	NM_024966.3		c.*362C>T		3_prime_UTR	Exon 13 of 13	NP_079242.2
	SEMA6D	NM_001358352.2		c.1427+366C>T		intron	N/A	NP_001345281.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEMA6D	ENST00000389425.7	TSL:1	c.*362C>T		3_prime_UTR	Exon 13 of 13	ENSP00000374076.3	Q8NFY4-7
	SEMA6D	ENST00000536845.7	TSL:2 MANE Select	c.1427+366C>T		intron	N/A	ENSP00000446152.3	Q8NFY4-1
	SEMA6D	ENST00000316364.9	TSL:1	c.1427+366C>T		intron	N/A	ENSP00000324857.5	Q8NFY4-1

Frequencies

GnomAD3 genomes AF: 0.639 AC: 96745 AN: 151496 Hom.: 31183 Cov.: 30

Gnomad AFR AF: 0.667

Gnomad AMI AF: 0.524

Gnomad AMR AF: 0.645

Gnomad ASJ AF: 0.604

Gnomad EAS AF: 0.760

Gnomad SAS AF: 0.626

Gnomad FIN AF: 0.721

Gnomad MID AF: 0.582

Gnomad NFE AF: 0.602

Gnomad OTH AF: 0.640

GnomAD4 exome AF: 0.593 AC: 517968 AN: 872896 Hom.: 154581 Cov.: 23 AF XY: 0.595 AC XY: 241106 AN XY: 405344

African (AFR) AF: 0.666 AC: 11320 AN: 16988

American (AMR) AF: 0.660 AC: 2520 AN: 3820

Ashkenazi Jewish (ASJ) AF: 0.592 AC: 3951 AN: 6672

East Asian (EAS) AF: 0.756 AC: 4675 AN: 6184

South Asian (SAS) AF: 0.613 AC: 11522 AN: 18804

European-Finnish (FIN) AF: 0.688 AC: 1544 AN: 2244

Middle Eastern (MID) AF: 0.583 AC: 1060 AN: 1818

European-Non Finnish (NFE) AF: 0.589 AC: 463031 AN: 786410

Other (OTH) AF: 0.612 AC: 18345 AN: 29956

GnomAD4 genome AF: 0.639 AC: 96814 AN: 151612 Hom.: 31210 Cov.: 30 AF XY: 0.647 AC XY: 47910 AN XY: 74056

African (AFR) AF: 0.666 AC: 27529 AN: 41304

American (AMR) AF: 0.646 AC: 9839 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.604 AC: 2096 AN: 3472

East Asian (EAS) AF: 0.760 AC: 3911 AN: 5148

South Asian (SAS) AF: 0.626 AC: 2996 AN: 4786

European-Finnish (FIN) AF: 0.721 AC: 7567 AN: 10494

Middle Eastern (MID) AF: 0.578 AC: 170 AN: 294

European-Non Finnish (NFE) AF: 0.602 AC: 40879 AN: 67860

Other (OTH) AF: 0.639 AC: 1350 AN: 2112

Alfa AF: 0.600 Hom.: 24198

Bravo AF: 0.634

Asia WGS AF: 0.691 AC: 2402 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.86
DANN	Benign	0.25
PhyloP100		-0.70
Mutation Taster		=100/0	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: rs537052; hg19: chr15-48057619;