chr13-83880243-AG-A

Variant names:

• chr13-83880243-AG-A
• rs193302861
• NM_001281503.2:c.1264delC

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP5

The NM_001281503.2(SLITRK1):​c.1264delC​(p.Leu422PhefsTer28) 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
• Publications: 7 publications found

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]

SLITRK1 Gene-Disease associations (from GenCC):

• Tourette syndrome

  Inheritance: Unknown, AD Classification: LIMITED, NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, Ambry Genetics
• trichotillomania

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ENSG00000285680 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 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 VariationId is 1578.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001281503.2. 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
	SLITRK1	NM_001281503.2	MANE Select	c.1264delC	p.Leu422PhefsTer28	frameshift	Exon 2 of 2	NP_001268432.1	Q96PX8
	SLITRK1	NM_052910.2		c.1264delC	p.Leu422PhefsTer28	frameshift	Exon 1 of 1	NP_443142.1	Q96PX8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLITRK1	ENST00000674365.1	MANE Select	c.1264delC	p.Leu422PhefsTer28	frameshift	Exon 2 of 2	ENSP00000501349.1	Q96PX8
	SLITRK1	ENST00000377084.3	TSL:6	c.1264delC	p.Leu422PhefsTer28	frameshift	Exon 1 of 1	ENSP00000366288.2	Q96PX8
	ENSG00000285680	ENST00000649183.1		n.201+1435delG		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Pathogenic

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
1	-	-	Tourette syndrome (2)
1	-	-	Trichotillomania (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		10
Mutation Taster		=11/189	disease causing (ClinVar)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs193302861; hg19: chr13-84454378;