rs17080147

chr13-85795268-T-C

Variant summary

Our verdict is Benign. Variant got -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. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• 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:4
• Conservation: PhyloP100: 6.28

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLITRK6	NM_032229.3	c.1241A>G	p.Gln414Arg	missense_variant	2/2	ENST00000647374.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLITRK6	ENST00000647374.2	c.1241A>G	p.Gln414Arg	missense_variant	2/2		NM_032229.3	P1
SLITRK6	ENST00000643778.1	c.1241A>G	p.Gln414Arg	missense_variant	3/3			P1

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

GnomAD3 exomes AF: 0.0264 AC: 6548 AN: 248254 Hom.: 717 AF XY: 0.0228 AC XY: 3074 AN XY: 134732

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 SAS exome AF: 0.0425

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

Gnomad4 AFR exome AF: 0.303

Gnomad4 AMR exome AF: 0.0156

Gnomad4 ASJ exome AF: 0.0000384

Gnomad4 EAS exome AF: 0.00532

Gnomad4 SAS exome AF: 0.0420

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000445

Gnomad4 OTH exome AF: 0.0220

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

Gnomad4 AFR AF: 0.285

Gnomad4 AMR AF: 0.0311

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00272

Gnomad4 SAS AF: 0.0443

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000795

Gnomad4 OTH AF: 0.0620

Alfa AF: 0.0159 Hom.: 599

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

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Aug 23, 2017	p.Gln414Arg in exon 2 of SLITRK6: This variant is not expected to have clinical significance because it has been identified in 29.28% (2864/9782) of African chr omosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.o rg; dbSNP rs17080147). -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 09, 2017	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	May 23, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 30, 2024	- -

Computational scores

Source: dbNSFP v4.3

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;T;T
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.43
FATHMM_MKL	Uncertain	0.96	D
MetaRNN	Benign	0.0017	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	L;L;L
MutationTaster	Benign	0.083	P
PrimateAI	Uncertain	0.51	T
Polyphen		0.48	P;P;P
Vest4		0.14
MPC		0.074
ClinPred		0.032	T
GERP RS		4.4
Varity_R		0.12
gMVP		0.44

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

Publications

LitVar

Other links and lift over

dbSNP: rs17080147; hg19: chr13-86369403;