rs12863734

Positions:

chr13-85796436-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_032229.3(SLITRK6):c.73C>T(p.Leu25Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.016 in 1,608,624 control chromosomes in the GnomAD database, including 225 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.018 ( 28 hom., cov: 32)

Exomes 𝑓: 0.016 ( 197 hom. )

Consequence

SLITRK6
NM_032229.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.0100

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:

SLITRK6 (HGNC:):

SLITRK6 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006147355).

BP6

Variant 13-85796436-G-A is Benign according to our data. Variant chr13-85796436-G-A is described in ClinVar as [Benign]. Clinvar id is 506093.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0182 (2772/151944) while in subpopulation AMR AF= 0.0256 (388/15180). AF 95% confidence interval is 0.0235. There are 28 homozygotes in gnomad4. There are 1369 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 28 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLITRK6	NM_032229.3 linkuse as main transcript	c.73C>T	p.Leu25Phe	missense_variant	2/2	ENST00000647374.2	NP_115605.2	Q9H5Y7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLITRK6	ENST00000647374.2 linkuse as main transcript	c.73C>T	p.Leu25Phe	missense_variant	2/2	NM_032229.3	ENSP00000495507.1	Q9H5Y7
SLITRK6	ENST00000643778.1 linkuse as main transcript	c.73C>T	p.Leu25Phe	missense_variant	3/3		ENSP00000496428.1	Q9H5Y7
SLITRK6	ENST00000645642.1 linkuse as main transcript	n.521-493C>T		intron_variant

Frequencies

GnomAD3 genomes

AF:

0.0182

AC:

2761

AN:

151826

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0214

Gnomad AMI

AF:

0.00548

Gnomad AMR

AF:

0.0257

Gnomad ASJ

AF:

0.0112

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00290

Gnomad FIN

AF:

0.0188

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0175

Gnomad OTH

AF:

0.0183

GnomAD3 exomes

AF:

0.0154

AC:

3746

AN:

243532

Hom.:

AF XY:

0.0144

AC XY:

1907

AN XY:

132162

show subpopulations

Gnomad AFR exome

AF:

0.0219

Gnomad AMR exome

AF:

0.0270

Gnomad ASJ exome

AF:

0.0104

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00283

Gnomad FIN exome

AF:

0.0175

Gnomad NFE exome

AF:

0.0169

Gnomad OTH exome

AF:

0.0125

GnomAD4 exome

AF:

0.0157

AC:

22938

AN:

1456680

Hom.:

197

Cov.:

AF XY:

0.0151

AC XY:

10945

AN XY:

724612

show subpopulations

Gnomad4 AFR exome

AF:

0.0211

Gnomad4 AMR exome

AF:

0.0255

Gnomad4 ASJ exome

AF:

0.0106

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00390

Gnomad4 FIN exome

AF:

0.0168

Gnomad4 NFE exome

AF:

0.0168

Gnomad4 OTH exome

AF:

0.0157

GnomAD4 genome

AF:

0.0182

AC:

2772

AN:

151944

Hom.:

Cov.:

AF XY:

0.0184

AC XY:

1369

AN XY:

74286

show subpopulations

Gnomad4 AFR

AF:

0.0216

Gnomad4 AMR

AF:

0.0256

Gnomad4 ASJ

AF:

0.0112

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00290

Gnomad4 FIN

AF:

0.0188

Gnomad4 NFE

AF:

0.0175

Gnomad4 OTH

AF:

0.0181

Alfa

AF:

0.0161

Hom.:

Bravo

AF:

0.0187

TwinsUK

AF:

0.0138

AC:

ALSPAC

AF:

0.0161

AC:

ESP6500AA

AF:

0.0229

AC:

ESP6500EA

AF:

0.0178

AC:

146

ExAC

AF:

0.0147

AC:

1771

Asia WGS

AF:

0.00549

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Jul 12, 2019	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 04, 2019	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Aug 23, 2017

p.Leu25Phe in exon 2 of SLITRK6: This variant is not expected to have clinical s ignificance because it has been identified in 2.59% (294/11348) of Latino chromo somes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs12863734). -

SLITRK6-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 15, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.054

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.69

CADD

Benign

3.1

DANN

Benign

0.91

DEOGEN2

Benign

0.074

T;T;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.041

LIST_S2

Benign

0.15

.;.;T

MetaRNN

Benign

0.0061

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.90

L;L;L

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.44

.;N;.

REVEL

Benign

0.050

Sift

Benign

0.11

.;T;.

Sift4G

Benign

0.71

.;T;.

Polyphen

0.0

B;B;B

Vest4

0.0050

MPC

0.048

ClinPred

0.00044

GERP RS

0.88

Varity_R

0.034

gMVP

0.44

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