15-47763910-C-T

Variant names:

• chr15-47763910-C-T
• NM_001358351.3:c.808C>T
• SEMA6D p.Leu270Leu

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001358351.3(SEMA6D):​c.808C>T​(p.Leu270Leu) variant causes a synonymous change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. L270L) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SEMA6D NM_001358351.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.17
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.21).

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.808C>T	p.Leu270Leu	synonymous	Exon 10 of 19	NP_001345280.1	Q8NFY4-1
	SEMA6D	NM_001358352.2		c.808C>T	p.Leu270Leu	synonymous	Exon 10 of 19	NP_001345281.1
	SEMA6D	NM_153618.2		c.808C>T	p.Leu270Leu	synonymous	Exon 10 of 19	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.808C>T	p.Leu270Leu	synonymous	Exon 10 of 19	ENSP00000446152.3	Q8NFY4-1
	SEMA6D	ENST00000316364.9	TSL:1	c.808C>T	p.Leu270Leu	synonymous	Exon 10 of 19	ENSP00000324857.5	Q8NFY4-1
	SEMA6D	ENST00000354744.8	TSL:1	c.808C>T	p.Leu270Leu	synonymous	Exon 10 of 18	ENSP00000346786.4	Q8NFY4-4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.21
CADD	Benign	11
DANN	Benign	0.75
PhyloP100		4.2

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

hg19: chr15-48056107;