13-83882600-T-C

Variant names:

• chr13-83882600-T-C
• rs9546538
• ENST00000654693.1:n.145T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000654693.1(ENSG00000285680):​n.145T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.28 in 152,032 control chromosomes in the GnomAD database, including 6,146 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.28 (6146 hom., cov: 32)
• Consequence: ENSG00000285680 ENST00000654693.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0270
• Publications: 13 publications found

Genes affected

ENSG00000285680 (HGNC:):

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

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.377 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLITRK1	NM_001281503.2	c.-650A>G		upstream_gene_variant		ENST00000674365.1	NP_001268432.1
SLITRK1	NM_052910.2	c.-1093A>G		upstream_gene_variant			NP_443142.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLITRK1	ENST00000674365.1	c.-650A>G		upstream_gene_variant			NM_001281503.2	ENSP00000501349.1

Frequencies

GnomAD3 genomes AF: 0.280 AC: 42563 AN: 151914 Hom.: 6136 Cov.: 32

Gnomad AFR AF: 0.288

Gnomad AMI AF: 0.283

Gnomad AMR AF: 0.319

Gnomad ASJ AF: 0.344

Gnomad EAS AF: 0.392

Gnomad SAS AF: 0.390

Gnomad FIN AF: 0.170

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.264

Gnomad OTH AF: 0.298

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.280 AC: 42604 AN: 152032 Hom.: 6146 Cov.: 32 AF XY: 0.279 AC XY: 20760 AN XY: 74308

African (AFR) AF: 0.288 AC: 11930 AN: 41466

American (AMR) AF: 0.319 AC: 4879 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.344 AC: 1192 AN: 3468

East Asian (EAS) AF: 0.392 AC: 2018 AN: 5154

South Asian (SAS) AF: 0.389 AC: 1868 AN: 4804

European-Finnish (FIN) AF: 0.170 AC: 1797 AN: 10590

Middle Eastern (MID) AF: 0.306 AC: 90 AN: 294

European-Non Finnish (NFE) AF: 0.264 AC: 17937 AN: 67954

Other (OTH) AF: 0.301 AC: 635 AN: 2112

Alfa AF: 0.272 Hom.: 9700

Bravo AF: 0.289

Asia WGS AF: 0.377 AC: 1309 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	11
DANN	Benign	0.64
PhyloP100		-0.027
PromoterAI		0.016	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs9546538; hg19: chr13-84456735;