rs431057

Variant names:

• chr13-85798128-A-C
• rs431057
• NM_032229.3:c.-25+786T>G

Your query was ambiguous. Multiple possible variants found:

• chr13-85798128-A-C
• chr13-85798128-A-G
• chr13-85798128-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032229.3(SLITRK6):​c.-25+786T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.625 in 151,584 control chromosomes in the GnomAD database, including 29,740 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.62 (29740 hom., cov: 31)
• Consequence: SLITRK6 NM_032229.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.460
• Publications: 3 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.745 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.-25+786T>G		intron	N/A	NP_115605.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLITRK6	ENST00000647374.2	MANE Select	c.-25+786T>G		intron	N/A	ENSP00000495507.1	Q9H5Y7
	SLITRK6	ENST00000643778.1		c.-25+786T>G		intron	N/A	ENSP00000496428.1	Q9H5Y7
	SLITRK6	ENST00000645642.1		n.520+786T>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.625 AC: 94606 AN: 151466 Hom.: 29700 Cov.: 31

Gnomad AFR AF: 0.608

Gnomad AMI AF: 0.428

Gnomad AMR AF: 0.683

Gnomad ASJ AF: 0.578

Gnomad EAS AF: 0.764

Gnomad SAS AF: 0.753

Gnomad FIN AF: 0.616

Gnomad MID AF: 0.604

Gnomad NFE AF: 0.608

Gnomad OTH AF: 0.644

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.625 AC: 94711 AN: 151584 Hom.: 29740 Cov.: 31 AF XY: 0.631 AC XY: 46730 AN XY: 74098

African (AFR) AF: 0.608 AC: 25169 AN: 41386

American (AMR) AF: 0.683 AC: 10356 AN: 15160

Ashkenazi Jewish (ASJ) AF: 0.578 AC: 2001 AN: 3464

East Asian (EAS) AF: 0.765 AC: 3921 AN: 5128

South Asian (SAS) AF: 0.754 AC: 3632 AN: 4820

European-Finnish (FIN) AF: 0.616 AC: 6502 AN: 10558

Middle Eastern (MID) AF: 0.626 AC: 184 AN: 294

European-Non Finnish (NFE) AF: 0.608 AC: 41200 AN: 67760

Other (OTH) AF: 0.645 AC: 1356 AN: 2102

Alfa AF: 0.612 Hom.: 50725

Bravo AF: 0.623

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.2
DANN	Benign	0.65
PhyloP100		0.46
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: rs431057; hg19: chr13-86372263;