rs35119660

Positions:

chr13-85796182-A-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_032229.3(SLITRK6):c.327T>C(p.Asn109=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0166 in 1,613,044 control chromosomes in the GnomAD database, including 251 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.021 ( 38 hom., cov: 32)

Exomes 𝑓: 0.016 ( 213 hom. )

Consequence

SLITRK6
NM_032229.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.89

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP6

Variant 13-85796182-A-G is Benign according to our data. Variant chr13-85796182-A-G is described in ClinVar as [Benign]. Clinvar id is 506091.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.89 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0212 (3217/152046) while in subpopulation AFR AF= 0.032 (1327/41526). AF 95% confidence interval is 0.0305. There are 38 homozygotes in gnomad4. There are 1568 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 38 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLITRK6	NM_032229.3 linkuse as main transcript	c.327T>C	p.Asn109=	synonymous_variant	2/2	ENST00000647374.2	NP_115605.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	Appris
SLITRK6	ENST00000647374.2 linkuse as main transcript	c.327T>C	p.Asn109=	synonymous_variant	2/2	NM_032229.3	ENSP00000495507	P1
SLITRK6	ENST00000643778.1 linkuse as main transcript	c.327T>C	p.Asn109=	synonymous_variant	3/3		ENSP00000496428	P1
SLITRK6	ENST00000645642.1 linkuse as main transcript	n.521-239T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.0211

AC:

3206

AN:

151928

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0317

Gnomad AMI

AF:

0.00548

Gnomad AMR

AF:

0.0266

Gnomad ASJ

AF:

0.0112

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00290

Gnomad FIN

AF:

0.0187

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0175

Gnomad OTH

AF:

0.0201

GnomAD3 exomes

AF:

0.0160

AC:

3978

AN:

248034

Hom.:

AF XY:

0.0149

AC XY:

2004

AN XY:

134544

show subpopulations

Gnomad AFR exome

AF:

0.0334

Gnomad AMR exome

AF:

0.0273

Gnomad ASJ exome

AF:

0.0101

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00278

Gnomad FIN exome

AF:

0.0173

Gnomad NFE exome

AF:

0.0169

Gnomad OTH exome

AF:

0.0125

GnomAD4 exome

AF:

0.0161

AC:

23512

AN:

1460998

Hom.:

213

Cov.:

AF XY:

0.0154

AC XY:

11198

AN XY:

726794

show subpopulations

Gnomad4 AFR exome

AF:

0.0335

Gnomad4 AMR exome

AF:

0.0258

Gnomad4 ASJ exome

AF:

0.0106

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00393

Gnomad4 FIN exome

AF:

0.0167

Gnomad4 NFE exome

AF:

0.0168

Gnomad4 OTH exome

AF:

0.0163

GnomAD4 genome

AF:

0.0212

AC:

3217

AN:

152046

Hom.:

Cov.:

AF XY:

0.0211

AC XY:

1568

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.0320

Gnomad4 AMR

AF:

0.0265

Gnomad4 ASJ

AF:

0.0112

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00290

Gnomad4 FIN

AF:

0.0187

Gnomad4 NFE

AF:

0.0175

Gnomad4 OTH

AF:

0.0199

Alfa

AF:

0.0186

Hom.:

Bravo

AF:

0.0222

Asia WGS

AF:

0.00607

AC:

AN:

3476

EpiCase

AF:

0.0141

EpiControl

AF:

0.0131

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

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

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 02, 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. -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Aug 23, 2017	p.Asn109Asn 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 3.06% (300/9794) o f African chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.bro adinstitute.org; dbSNP rs35119660). -

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

BayesDel_noAF

Benign

-0.53

CADD

Benign

4.6

DANN

Benign

0.63

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