rs35342386

Variant names:

• chr13-85796287-G-A
• rs35342386
• NM_032229.3:c.222C>T

Your query was ambiguous. Multiple possible variants found:

• chr13-85796287-G-A
• chr13-85796287-G-T

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.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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 1.49
• Publications: 6 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=-0.54).
• 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

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.222C>T	p.Asn74Asn	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.222C>T	p.Asn74Asn	synonymous	Exon 2 of 2	ENSP00000495507.1	Q9H5Y7
	SLITRK6	ENST00000643778.1		c.222C>T	p.Asn74Asn	synonymous	Exon 3 of 3	ENSP00000496428.1	Q9H5Y7
	SLITRK6	ENST00000645642.1		n.521-344C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0212 AC: 3224 AN: 151866 Hom.: 37 Cov.: 32

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

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.: 35 AF XY: 0.0154 AC XY: 11189 AN XY: 725972

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: 2 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: 33 AN: 5746

European-Non Finnish (NFE) AF: 0.0168 AC: 18709 AN: 1110796

Other (OTH) AF: 0.0163 AC: 982 AN: 60284

GnomAD4 genome AF: 0.0213 AC: 3235 AN: 151982 Hom.: 38 Cov.: 32 AF XY: 0.0212 AC XY: 1577 AN XY: 74288

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: 39 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5158

South Asian (SAS) AF: 0.00290 AC: 14 AN: 4824

European-Finnish (FIN) AF: 0.0188 AC: 199 AN: 10604

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0175 AC: 1190 AN: 67934

Other (OTH) AF: 0.0199 AC: 42 AN: 2106

Alfa AF: 0.0187 Hom.: 15

Bravo AF: 0.0223

Asia WGS AF: 0.00549 AC: 19 AN: 3478

EpiCase AF: 0.0140

EpiControl AF: 0.0131

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	not specified (2)
-	-	1	SLITRK6-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	7.2
DANN	Benign	0.63
PhyloP100		1.5
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: rs35342386; hg19: chr13-86370422; COSMIC: COSV68390225;