13-85798128-A-G

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_032229.3(SLITRK6):​c.-25+786T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).

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>C		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>C		intron	N/A	ENSP00000495507.1	Q9H5Y7
	SLITRK6	ENST00000643778.1		c.-25+786T>C		intron	N/A	ENSP00000496428.1	Q9H5Y7
	SLITRK6	ENST00000645642.1		n.520+786T>C		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 31

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

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 50725

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.6
DANN	Benign	0.62
PhyloP100		0.46

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;