rs35119660

Variant names:

• chr13-85796182-A-G
• rs35119660
• NM_032229.3:c.327T>C

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.327T>C​(p.Asn109Asn) 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 1,613,044 control chromosomes in the GnomAD database, including 251 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 (213 hom.)
• Consequence: SLITRK6 NM_032229.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 1.89
• Publications: 4 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, PanelApp Australia, G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen
• 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=-0.53).
• BP6: Variant 13-85796182-A-G is Benign according to our data. Variant chr13-85796182-A-G is described in ClinVar as Benign. ClinVar VariationId is 506091.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.89 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0212 (3217/152046) while in subpopulation AFR AF = 0.032 (1327/41526). AF 95% confidence interval is 0.0305. There are 38 homozygotes in GnomAd4. There are 1568 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.327T>C	p.Asn109Asn	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.327T>C	p.Asn109Asn	synonymous	Exon 2 of 2	ENSP00000495507.1	Q9H5Y7
	SLITRK6	ENST00000643778.1		c.327T>C	p.Asn109Asn	synonymous	Exon 3 of 3	ENSP00000496428.1	Q9H5Y7
	SLITRK6	ENST00000645642.1		n.521-239T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0211 AC: 3206 AN: 151928 Hom.: 37 Cov.: 32

Gnomad AFR AF: 0.0317

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.0266

Gnomad ASJ AF: 0.0112

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00290

Gnomad FIN AF: 0.0187

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0175

Gnomad OTH AF: 0.0201

GnomAD2 exomes AF: 0.0160 AC: 3978 AN: 248034 AF XY: 0.0149

Gnomad AFR exome AF: 0.0334

Gnomad AMR exome AF: 0.0273

Gnomad ASJ exome AF: 0.0101

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0173

Gnomad NFE exome AF: 0.0169

Gnomad OTH exome AF: 0.0125

GnomAD4 exome AF: 0.0161 AC: 23512 AN: 1460998 Hom.: 213 Cov.: 35 AF XY: 0.0154 AC XY: 11198 AN XY: 726794

African (AFR) AF: 0.0335 AC: 1121 AN: 33434

American (AMR) AF: 0.0258 AC: 1153 AN: 44624

Ashkenazi Jewish (ASJ) AF: 0.0106 AC: 276 AN: 26070

East Asian (EAS) AF: 0.00 AC: 0 AN: 39670

South Asian (SAS) AF: 0.00393 AC: 339 AN: 86224

European-Finnish (FIN) AF: 0.0167 AC: 893 AN: 53382

Middle Eastern (MID) AF: 0.00556 AC: 32 AN: 5754

European-Non Finnish (NFE) AF: 0.0168 AC: 18713 AN: 1111498

Other (OTH) AF: 0.0163 AC: 985 AN: 60342

GnomAD4 genome AF: 0.0212 AC: 3217 AN: 152046 Hom.: 38 Cov.: 32 AF XY: 0.0211 AC XY: 1568 AN XY: 74338

African (AFR) AF: 0.0320 AC: 1327 AN: 41526

American (AMR) AF: 0.0265 AC: 402 AN: 15192

Ashkenazi Jewish (ASJ) AF: 0.0112 AC: 39 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5160

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

European-Finnish (FIN) AF: 0.0187 AC: 199 AN: 10616

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

European-Non Finnish (NFE) AF: 0.0175 AC: 1187 AN: 67942

Other (OTH) AF: 0.0199 AC: 42 AN: 2112

Alfa AF: 0.0187 Hom.: 15

Bravo AF: 0.0222

Asia WGS AF: 0.00607 AC: 21 AN: 3476

EpiCase AF: 0.0141

EpiControl AF: 0.0131

ClinVar

ClinVar submissions as Germline

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	-0.53
CADD	Benign	4.6
DANN	Benign	0.63
PhyloP100		1.9
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: rs35119660; hg19: chr13-86370317;