chr13-85796470-A-T

Variant names:

• chr13-85796470-A-T
• rs74104527
• NM_032229.3:c.39T>A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_032229.3(SLITRK6):​c.39T>A​(p.Leu13Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00139 in 1,575,392 control chromosomes in the GnomAD database, including 36 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0080 (23 hom., cov: 32)
  • Exomes 𝑓: 0.00069 (13 hom.)
• Consequence: SLITRK6 NM_032229.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.277

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]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 13-85796470-A-T is Benign according to our data. Variant chr13-85796470-A-T is described in ClinVar as [Benign]. Clinvar id is 506094.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-85796470-A-T is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=0.277 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00801 (1217/151978) while in subpopulation AFR AF= 0.0272 (1129/41514). AF 95% confidence interval is 0.0259. There are 23 homozygotes in gnomad4. There are 576 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 23 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLITRK6	NM_032229.3	c.39T>A	p.Leu13Leu	synonymous_variant	Exon 2 of 2	ENST00000647374.2	NP_115605.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLITRK6	ENST00000647374.2	c.39T>A	p.Leu13Leu	synonymous_variant	Exon 2 of 2		NM_032229.3	ENSP00000495507.1
SLITRK6	ENST00000643778.1	c.39T>A	p.Leu13Leu	synonymous_variant	Exon 3 of 3			ENSP00000496428.1
SLITRK6	ENST00000645642.1	n.521-527T>A		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.00802 AC: 1218 AN: 151860 Hom.: 24 Cov.: 32

Gnomad AFR AF: 0.0273

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00488

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000442

Gnomad OTH AF: 0.00480

GnomAD3 exomes AF: 0.00214 AC: 453 AN: 211436 Hom.: 5 AF XY: 0.00157 AC XY: 180 AN XY: 114904

Gnomad AFR exome AF: 0.0274

Gnomad AMR exome AF: 0.00150

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000298

Gnomad OTH exome AF: 0.00163

GnomAD4 exome AF: 0.000688 AC: 980 AN: 1423414 Hom.: 13 Cov.: 34 AF XY: 0.000570 AC XY: 403 AN XY: 706748

Gnomad4 AFR exome AF: 0.0258

Gnomad4 AMR exome AF: 0.00185

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000251

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000455

Gnomad4 OTH exome AF: 0.00162

GnomAD4 genome AF: 0.00801 AC: 1217 AN: 151978 Hom.: 23 Cov.: 32 AF XY: 0.00775 AC XY: 576 AN XY: 74304

Gnomad4 AFR AF: 0.0272

Gnomad4 AMR AF: 0.00487

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000442

Gnomad4 OTH AF: 0.00475

Alfa AF: 0.00445 Hom.: 3

Bravo AF: 0.00963

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

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.Leu13Leu 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 2.83% (264/9342) of African chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broa dinstitute.org; dbSNP rs74104527). -

Mar 05, 2018

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

Dec 02, 2024

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

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.61
DANN	Benign	0.41

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

Other links and lift over

dbSNP: rs74104527; hg19: chr13-86370605;