13-85794985-C-T

Variant names:

• chr13-85794985-C-T
• rs3825413
• NM_032229.3:c.1524G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.0480
• Publications: 25 publications found

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: Orphanet, Labcorp Genetics (formerly Invitae), PanelApp Australia, ClinGen, Ambry Genetics, G2P
• hearing loss, autosomal recessive

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032229.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLITRK6	NM_032229.3	MANE Select	c.1524G>A	p.Leu508Leu	synonymous	Exon 2 of 2	NP_115605.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLITRK6	ENST00000647374.2	MANE Select	c.1524G>A	p.Leu508Leu	synonymous	Exon 2 of 2	ENSP00000495507.1	Q9H5Y7
	SLITRK6	ENST00000643778.1		c.1524G>A	p.Leu508Leu	synonymous	Exon 3 of 3	ENSP00000496428.1	Q9H5Y7

Frequencies

GnomAD3 genomes AF: 0.763 AC: 115690 AN: 151610 Hom.: 44577 Cov.: 30

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

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.: 64 AF XY: 0.728 AC XY: 528949 AN XY: 726786

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

GnomAD4 genome AF: 0.763 AC: 115813 AN: 151728 Hom.: 44635 Cov.: 30 AF XY: 0.765 AC XY: 56702 AN XY: 74112

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

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

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	2	not specified (2)
-	-	1	High myopia-sensorineural deafness syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	3.1
DANN	Benign	0.62
PhyloP100		0.048
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3825413; hg19: chr13-86369120; COSMIC: COSV68389233; COSMIC: COSV68389233;