NM_001281503.2:c.*2042T>A

Variant names:

• chr13-83877375-A-T
• rs1046202
• NM_001281503.2:c.*2042T>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 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)

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

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.*2042T>A		3_prime_UTR	Exon 2 of 2	NP_001268432.1	Q96PX8
	SLITRK1	NM_052910.2		c.*2042T>A		3_prime_UTR	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.*2042T>A		3_prime_UTR	Exon 2 of 2	ENSP00000501349.1	Q96PX8
	SLITRK1	ENST00000377084.3	TSL:6	c.*2042T>A		3_prime_UTR	Exon 1 of 1	ENSP00000366288.2	Q96PX8

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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 1 AN: 2

Other (OTH) AC: 0 AN: 0

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

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

African (AFR) AF: 0.450 AC: 4541 AN: 10100

American (AMR) AF: 0.328 AC: 4253 AN: 12984

Ashkenazi Jewish (ASJ) AF: 0.335 AC: 1071 AN: 3194

East Asian (EAS) AF: 0.443 AC: 1954 AN: 4408

South Asian (SAS) AF: 0.401 AC: 1847 AN: 4610

European-Finnish (FIN) AF: 0.151 AC: 1526 AN: 10116

Middle Eastern (MID) AF: 0.289 AC: 70 AN: 242

European-Non Finnish (NFE) AF: 0.252 AC: 16507 AN: 65394

Other (OTH) AF: 0.315 AC: 504 AN: 1602

Alfa AF: 0.216 Hom.: 386

Asia WGS AF: 0.384 AC: 1224 AN: 3192

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	Tourette syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.10
DANN	Benign	0.27
PhyloP100		-1.6
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: rs1046202; hg19: chr13-84451510;