rs74104527

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 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=-0.86).
• BP6: Variant 13-85796470-A-T is Benign according to our data. Variant chr13-85796470-A-T is described in ClinVar as Benign. ClinVar VariationId is 506094.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 23 AR gene

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.39T>A	p.Leu13Leu	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.39T>A	p.Leu13Leu	synonymous	Exon 2 of 2	ENSP00000495507.1	Q9H5Y7
	SLITRK6	ENST00000643778.1		c.39T>A	p.Leu13Leu	synonymous	Exon 3 of 3	ENSP00000496428.1	Q9H5Y7
	SLITRK6	ENST00000645642.1		n.521-527T>A		intron	N/A

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

GnomAD2 exomes AF: 0.00214 AC: 453 AN: 211436 AF XY: 0.00157

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 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

African (AFR) AF: 0.0258 AC: 811 AN: 31412

American (AMR) AF: 0.00185 AC: 65 AN: 35048

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23428

East Asian (EAS) AF: 0.00 AC: 0 AN: 39404

South Asian (SAS) AF: 0.0000251 AC: 2 AN: 79700

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52106

Middle Eastern (MID) AF: 0.000362 AC: 2 AN: 5520

European-Non Finnish (NFE) AF: 0.00000455 AC: 5 AN: 1098178

Other (OTH) AF: 0.00162 AC: 95 AN: 58618

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

African (AFR) AF: 0.0272 AC: 1129 AN: 41514

American (AMR) AF: 0.00487 AC: 74 AN: 15194

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5152

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000442 AC: 3 AN: 67900

Other (OTH) AF: 0.00475 AC: 10 AN: 2104

Alfa AF: 0.00445 Hom.: 3

Bravo AF: 0.00963

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	2	not specified (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.61
DANN	Benign	0.41
PhyloP100		0.28
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs74104527; hg19: chr13-86370605;