rs17080147

Variant names:

• chr13-85795268-T-C
• rs17080147
• NM_032229.3:c.1241A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_032229.3(SLITRK6):​c.1241A>G​(p.Gln414Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0182 in 1,612,632 control chromosomes in the GnomAD database, including 3,418 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.084 (1700 hom., cov: 32)
  • Exomes 𝑓: 0.011 (1718 hom.)
• Consequence: SLITRK6 NM_032229.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 6.28
• Publications: 9 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0017033517).
• BP6: Variant 13-85795268-T-C is Benign according to our data. Variant chr13-85795268-T-C is described in ClinVar as Benign. ClinVar VariationId is 506090.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.281 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.1241A>G	p.Gln414Arg	missense	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.1241A>G	p.Gln414Arg	missense	Exon 2 of 2	ENSP00000495507.1	Q9H5Y7
	SLITRK6	ENST00000643778.1		c.1241A>G	p.Gln414Arg	missense	Exon 3 of 3	ENSP00000496428.1	Q9H5Y7

Frequencies

GnomAD3 genomes AF: 0.0837 AC: 12707 AN: 151818 Hom.: 1701 Cov.: 32

Gnomad AFR AF: 0.286

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0311

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00272

Gnomad SAS AF: 0.0449

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000795

Gnomad OTH AF: 0.0627

GnomAD2 exomes AF: 0.0264 AC: 6548 AN: 248254 AF XY: 0.0228

Gnomad AFR exome AF: 0.296

Gnomad AMR exome AF: 0.0141

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00162

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000835

Gnomad OTH exome AF: 0.0122

GnomAD4 exome AF: 0.0113 AC: 16567 AN: 1460696 Hom.: 1718 Cov.: 35 AF XY: 0.0114 AC XY: 8318 AN XY: 726616

African (AFR) AF: 0.303 AC: 10128 AN: 33414

American (AMR) AF: 0.0156 AC: 694 AN: 44546

Ashkenazi Jewish (ASJ) AF: 0.0000384 AC: 1 AN: 26072

East Asian (EAS) AF: 0.00532 AC: 211 AN: 39640

South Asian (SAS) AF: 0.0420 AC: 3623 AN: 86224

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53318

Middle Eastern (MID) AF: 0.0153 AC: 88 AN: 5756

European-Non Finnish (NFE) AF: 0.000445 AC: 495 AN: 1111422

Other (OTH) AF: 0.0220 AC: 1327 AN: 60304

GnomAD4 genome AF: 0.0837 AC: 12716 AN: 151936 Hom.: 1700 Cov.: 32 AF XY: 0.0828 AC XY: 6152 AN XY: 74286

African (AFR) AF: 0.285 AC: 11826 AN: 41446

American (AMR) AF: 0.0311 AC: 473 AN: 15212

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3462

East Asian (EAS) AF: 0.00272 AC: 14 AN: 5144

South Asian (SAS) AF: 0.0443 AC: 214 AN: 4828

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

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.000795 AC: 54 AN: 67910

Other (OTH) AF: 0.0620 AC: 131 AN: 2112

Alfa AF: 0.0318 Hom.: 1764

Bravo AF: 0.0946

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.273 AC: 1010

ESP6500EA AF: 0.00110 AC: 9

ExAC AF: 0.0313 AC: 3784

Asia WGS AF: 0.0410 AC: 142 AN: 3478

EpiCase AF: 0.000928

EpiControl AF: 0.000949

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	not specified (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.097
BayesDel_addAF	Benign	-0.58	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	18
DANN	Benign	0.12
DEOGEN2	Benign	0.062	T
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.43
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.65	T
MetaRNN	Benign	0.0017	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	L
PhyloP100		6.3
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	1.8	N
REVEL	Benign	0.14
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.48	P
Vest4		0.14
MPC		0.074
ClinPred		0.032	T
GERP RS		4.4
Varity_R		0.12
gMVP		0.44
Mutation Taster		=96/4	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: rs17080147; hg19: chr13-86369403;