13-85794985-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -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

Publications

25 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=-0.8).

BP6

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

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 rank	MANE	Protein	UniProt
SLITRK6	NM_032229.3 link	c.1524G>A	p.Leu508Leu	synonymous_variant	Exon 2 of 2	ENST00000647374.2	NP_115605.2	Q9H5Y7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLITRK6	ENST00000647374.2 link	c.1524G>A	p.Leu508Leu	synonymous_variant	Exon 2 of 2		NM_032229.3	ENSP00000495507.1		Q9H5Y7
SLITRK6	ENST00000643778.1 link	c.1524G>A	p.Leu508Leu	synonymous_variant	Exon 3 of 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

GnomAD2 exomes

AF:

0.715

AC:

177800

AN:

248686

AF XY:

0.715

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 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

African (AFR)

AF:

0.858

AC:

28694

AN:

33434

American (AMR)

AF:

0.603

AC:

26893

AN:

44588

Ashkenazi Jewish (ASJ)

AF:

0.571

AC:

14910

AN:

26090

East Asian (EAS)

AF:

0.671

AC:

26626

AN:

39676

South Asian (SAS)

AF:

0.682

AC:

58849

AN:

86236

European-Finnish (FIN)

AF:

0.832

AC:

44426

AN:

53384

Middle Eastern (MID)

AF:

0.562

AC:

3240

AN:

5762

European-Non Finnish (NFE)

AF:

0.736

AC:

818371

AN:

1111434

Other (OTH)

AF:

0.718

AC:

43302

AN:

60338

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

17987

35973

53960

71946

89933

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20096

40192

60288

80384

100480

<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:

0.763

AC:

115813

AN:

151728

Hom.:

44635

Cov.:

AF XY:

0.765

AC XY:

56702

AN XY:

74112

show subpopulations

African (AFR)

AF:

0.853

AC:

35362

AN:

41448

American (AMR)

AF:

0.680

AC:

10303

AN:

15160

Ashkenazi Jewish (ASJ)

AF:

0.560

AC:

1939

AN:

3460

East Asian (EAS)

AF:

0.695

AC:

3547

AN:

5102

South Asian (SAS)

AF:

0.687

AC:

3304

AN:

4808

European-Finnish (FIN)

AF:

0.847

AC:

8961

AN:

10582

Middle Eastern (MID)

AF:

0.619

AC:

182

AN:

294

European-Non Finnish (NFE)

AF:

0.736

AC:

49926

AN:

67858

Other (OTH)

AF:

0.733

AC:

1542

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1383

2766

4150

5533

6916

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

856

1712

2568

3424

4280

<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:

0.733

Hom.:

165784

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

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.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). -

May 09, 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. -

not provided

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

High myopia-sensorineural deafness syndrome

Benign:1

Jul 15, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

3.1

(source)

DANN

Benign

0.62

PhyloP100

0.048

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

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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