13-85794985-C-T

Position:

chr13-85794985-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_032229.3(SLITRK6):c.1524G>A(p.Leu508Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.732 in 1,612,670 control chromosomes in the GnomAD database, including 435,245 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.76 ( 44635 hom., cov: 30)

Exomes 𝑓: 0.73 ( 390610 hom. )

Consequence

SLITRK6
NM_032229.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.0480

Variant links:

Genes affected

SLITRK6 (HGNC:23503): (SLIT and NTRK like family member 6) 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. This protein functions as a regulator of neurite outgrowth required for normal hearing and vision. Mutations in this gene are a cause of myopia and deafness. [provided by RefSeq, Dec 2014]

SLITRK6 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 13-85794985-C-T is Benign according to our data. Variant chr13-85794985-C-T is described in ClinVar as [Benign]. Clinvar id is 506089.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-85794985-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.048 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.846 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLITRK6	NM_032229.3 link	c.1524G>A	p.Leu508Leu	synonymous_variant	2/2	ENST00000647374.2	NP_115605.2	Q9H5Y7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLITRK6	ENST00000647374.2 link	c.1524G>A	p.Leu508Leu	synonymous_variant	2/2		NM_032229.3	ENSP00000495507.1		Q9H5Y7
SLITRK6	ENST00000643778.1 link	c.1524G>A	p.Leu508Leu	synonymous_variant	3/3			ENSP00000496428.1		Q9H5Y7

Frequencies

GnomAD3 genomes

AF:

0.763

AC:

115690

AN:

151610

Hom.:

44577

Cov.:

show subpopulations

Gnomad AFR

AF:

0.853

Gnomad AMI

AF:

0.819

Gnomad AMR

AF:

0.680

Gnomad ASJ

AF:

0.560

Gnomad EAS

AF:

0.695

Gnomad SAS

AF:

0.688

Gnomad FIN

AF:

0.847

Gnomad MID

AF:

0.601

Gnomad NFE

AF:

0.736

Gnomad OTH

AF:

0.732

GnomAD3 exomes

AF:

0.715

AC:

177800

AN:

248686

Hom.:

64501

AF XY:

0.715

AC XY:

96498

AN XY:

134924

show subpopulations

Gnomad AFR exome

AF:

0.867

Gnomad AMR exome

AF:

0.593

Gnomad ASJ exome

AF:

0.571

Gnomad EAS exome

AF:

0.699

Gnomad SAS exome

AF:

0.685

Gnomad FIN exome

AF:

0.835

Gnomad NFE exome

AF:

0.733

Gnomad OTH exome

AF:

0.694

GnomAD4 exome

AF:

0.729

AC:

1065311

AN:

1460942

Hom.:

390610

Cov.:

AF XY:

0.728

AC XY:

528949

AN XY:

726786

show subpopulations

Gnomad4 AFR exome

AF:

0.858

Gnomad4 AMR exome

AF:

0.603

Gnomad4 ASJ exome

AF:

0.571

Gnomad4 EAS exome

AF:

0.671

Gnomad4 SAS exome

AF:

0.682

Gnomad4 FIN exome

AF:

0.832

Gnomad4 NFE exome

AF:

0.736

Gnomad4 OTH exome

AF:

0.718

GnomAD4 genome

AF:

0.763

AC:

115813

AN:

151728

Hom.:

44635

Cov.:

AF XY:

0.765

AC XY:

56702

AN XY:

74112

show subpopulations

Gnomad4 AFR

AF:

0.853

Gnomad4 AMR

AF:

0.680

Gnomad4 ASJ

AF:

0.560

Gnomad4 EAS

AF:

0.695

Gnomad4 SAS

AF:

0.687

Gnomad4 FIN

AF:

0.847

Gnomad4 NFE

AF:

0.736

Gnomad4 OTH

AF:

0.733

Alfa

AF:

0.724

Hom.:

76523

Bravo

AF:

0.752

Asia WGS

AF:

0.717

AC:

2496

AN:

3478

EpiCase

AF:

0.718

EpiControl

AF:

0.710

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Aug 23, 2017	p.Leu508Leu in exon 2 of SLITRK6: This variant is not expected to have clinical significance because it does not alter an amino acid residue, is not located wit hin the splice consensus sequence, and has been identified in 86.00% (8425/9796) of African chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.b roadinstitute.org; dbSNP rs3825413). -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 09, 2017	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

High myopia-sensorineural deafness syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

3.1

DANN

Benign

0.62

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over