rs35342386

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_032229.3(SLITRK6):c.222C>T(p.Asn74Asn) 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 1,611,612 control chromosomes in the GnomAD database, including 248 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 ( 210 hom. )

Consequence

SLITRK6
NM_032229.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.49

Publications

6 publications found

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 Gene-Disease associations (from GenCC):

high myopia-sensorineural deafness syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: ClinGen, PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics, Orphanet
hearing loss, autosomal recessive
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

SLITRK6 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP6

Variant 13-85796287-G-A is Benign according to our data. Variant chr13-85796287-G-A is described in ClinVar as Benign. ClinVar VariationId is 506092.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.49 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0213 (3235/151982) while in subpopulation AFR AF = 0.0324 (1345/41488). AF 95% confidence interval is 0.031. There are 38 homozygotes in GnomAd4. There are 1577 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 38 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLITRK6	NM_032229.3 link	c.222C>T	p.Asn74Asn	synonymous_variant	Exon 2 of 2	ENST00000647374.2	NP_115605.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
SLITRK6	ENST00000647374.2 link	c.222C>T	p.Asn74Asn	synonymous_variant	Exon 2 of 2	NM_032229.3	ENSP00000495507.1
SLITRK6	ENST00000643778.1 link	c.222C>T	p.Asn74Asn	synonymous_variant	Exon 3 of 3		ENSP00000496428.1
SLITRK6	ENST00000645642.1 link	n.521-344C>T		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.0212

AC:

3224

AN:

151866

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0322

Gnomad AMI

AF:

0.00548

Gnomad AMR

AF:

0.0264

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:

0.0202

GnomAD2 exomes

AF:

0.0161

AC:

3964

AN:

246878

AF XY:

0.0149

show subpopulations

Gnomad AFR exome

AF:

0.0337

Gnomad AMR exome

AF:

0.0269

Gnomad ASJ exome

AF:

0.0103

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0175

Gnomad NFE exome

AF:

0.0169

Gnomad OTH exome

AF:

0.0128

GnomAD4 exome

AF:

0.0161

AC:

23496

AN:

1459630

Hom.:

210

Cov.:

AF XY:

0.0154

AC XY:

11189

AN XY:

725972

show subpopulations

African (AFR)

AF:

0.0337

AC:

1125

AN:

33366

American (AMR)

AF:

0.0254

AC:

1133

AN:

44520

Ashkenazi Jewish (ASJ)

AF:

0.0106

AC:

275

AN:

25970

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39662

South Asian (SAS)

AF:

0.00395

AC:

340

AN:

85970

European-Finnish (FIN)

AF:

0.0168

AC:

897

AN:

53316

Middle Eastern (MID)

AF:

0.00574

AC:

AN:

5746

European-Non Finnish (NFE)

AF:

0.0168

AC:

18709

AN:

1110796

Other (OTH)

AF:

0.0163

AC:

982

AN:

60284

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.459

Heterozygous variant carriers

1297

2595

3892

5190

6487

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

722

1444

2166

2888

3610

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0213

AC:

3235

AN:

151982

Hom.:

Cov.:

AF XY:

0.0212

AC XY:

1577

AN XY:

74288

show subpopulations

African (AFR)

AF:

0.0324

AC:

1345

AN:

41488

American (AMR)

AF:

0.0263

AC:

399

AN:

15194

Ashkenazi Jewish (ASJ)

AF:

0.0112

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5158

South Asian (SAS)

AF:

0.00290

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.0188

AC:

199

AN:

10604

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0175

AC:

1190

AN:

67934

Other (OTH)

AF:

0.0199

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

166

332

498

664

830

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

108

144

180

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0187

Hom.:

Bravo

AF:

0.0223

Asia WGS

AF:

0.00549

AC:

AN:

3478

EpiCase

AF:

0.0140

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

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jul 12, 2019

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 29, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:2

Nov 02, 2017

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

Aug 23, 2017

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

p.Asn74Asn in exon 2 of SLITRK6: This variant is not expected to have clinical s ignificance because it does not alter an amino acid residue, is not located with in the splice consensus sequence, and has been identified in 3.12% (306/9798) of African chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broa dinstitute.org; dbSNP rs35342386). -

SLITRK6-related disorder

Benign:1

Jul 15, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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

-0.54

CADD

Benign

7.2

(source)

DANN

Benign

0.63

PhyloP100

1.5

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over