rs193302861

Positions:

• chr13-83880243-AG-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP5

The NM_001281503.2(SLITRK1):​c.1264delC​(p.Leu422fs) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 31)
• Consequence: SLITRK1 NM_001281503.2 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:2 O:1
• Conservation: PhyloP100: 10.0

Genes affected

SLITRK1 (HGNC:20297): (SLIT and NTRK like family member 1) This gene encodes a member of the SLITRK protein family. Members of this family are integral membrane proteins that are characterized by two N-terminal leucine-rich repeat (LRR) domains and a C-terminal region that shares homology with trk neurotrophin receptors. However, the protein encoded by this gene lacks the region of homology to neurotrophin receptors. This protein is thought to be involved in neurite outgrowth. Mutations in this gene may be associated with Tourette syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

ENSG00000285680 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 13-83880243-AG-A is Pathogenic according to our data. Variant chr13-83880243-AG-A is described in ClinVar as [Pathogenic]. Clinvar id is 1578.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLITRK1	NM_001281503.2	c.1264delC	p.Leu422fs	frameshift_variant	2/2	ENST00000674365.1	NP_001268432.1
SLITRK1	NM_052910.2	c.1264delC	p.Leu422fs	frameshift_variant	1/1		NP_443142.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLITRK1	ENST00000674365.1	c.1264delC	p.Leu422fs	frameshift_variant	2/2		NM_001281503.2	ENSP00000501349.1
SLITRK1	ENST00000377084.3	c.1264delC	p.Leu422fs	frameshift_variant	1/1	6		ENSP00000366288.2
ENSG00000285680	ENST00000649183.1	n.201+1435delG		intron_variant
ENSG00000285680	ENST00000667130.1	n.204+1435delG		intron_variant

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:2 Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Tourette syndrome Pathogenic:1 Other:1

not provided, no classification provided	literature only	GeneReviews	-	- -
Pathogenic, no assertion criteria provided	literature only	OMIM	Oct 14, 2005	- -

Trichotillomania Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Oct 14, 2005

- -

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs193302861; hg19: chr13-84454378;