13-83877375-A-T

Position:

• chr13-83877375-A-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001281503.2(SLITRK1):​c.*2042T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.286 in 113,430 control chromosomes in the GnomAD database, including 3,865 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.29 (3865 hom., cov: 29)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: SLITRK1 NM_001281503.2 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.58

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 13-83877375-A-T is Benign according to our data. Variant chr13-83877375-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 312477.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.439 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLITRK1	NM_001281503.2	c.*2042T>A		3_prime_UTR_variant	2/2	ENST00000674365.1	NP_001268432.1
SLITRK1	NM_052910.2	c.*2042T>A		3_prime_UTR_variant	1/1		NP_443142.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLITRK1	ENST00000674365	c.*2042T>A		3_prime_UTR_variant	2/2		NM_001281503.2	ENSP00000501349.1
SLITRK1	ENST00000377084	c.*2042T>A		3_prime_UTR_variant	1/1			ENSP00000366288.2

Frequencies

GnomAD3 genomes AF: 0.286 AC: 32430 AN: 113410 Hom.: 3861 Cov.: 29

Gnomad AFR AF: 0.450

Gnomad AMI AF: 0.213

Gnomad AMR AF: 0.327

Gnomad ASJ AF: 0.335

Gnomad EAS AF: 0.444

Gnomad SAS AF: 0.402

Gnomad FIN AF: 0.151

Gnomad MID AF: 0.302

Gnomad NFE AF: 0.252

Gnomad OTH AF: 0.311

GnomAD4 exome AF: 0.500 AC: 1 AN: 2 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

Gnomad4 NFE exome AF: 0.500

GnomAD4 genome AF: 0.286 AC: 32439 AN: 113428 Hom.: 3865 Cov.: 29 AF XY: 0.285 AC XY: 15864 AN XY: 55754

Gnomad4 AFR AF: 0.450

Gnomad4 AMR AF: 0.328

Gnomad4 ASJ AF: 0.335

Gnomad4 EAS AF: 0.443

Gnomad4 SAS AF: 0.401

Gnomad4 FIN AF: 0.151

Gnomad4 NFE AF: 0.252

Gnomad4 OTH AF: 0.315

Alfa AF: 0.216 Hom.: 386

Asia WGS AF: 0.384 AC: 1224 AN: 3192

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Tourette syndrome Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.10
DANN	Benign	0.27

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: rs1046202; hg19: chr13-84451510;