chr13-85794985-C-A

Variant names:

• chr13-85794985-C-A
• rs3825413
• NM_032229.3:c.1524G>T

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.1524G>T​(p.Leu508Phe) variant causes a missense 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. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. L508L) has been classified as Benign.

• Frequency: Genomes: not found (cov: 30)
• Consequence: SLITRK6 NM_032229.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0480
• Publications: 25 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: ClinGen, PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics, Orphanet
• 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 (MetaRNN=0.06605983).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLITRK6	NM_032229.3	MANE Select	c.1524G>T	p.Leu508Phe	missense	Exon 2 of 2	NP_115605.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLITRK6	ENST00000647374.2	MANE Select	c.1524G>T	p.Leu508Phe	missense	Exon 2 of 2	ENSP00000495507.1
	SLITRK6	ENST00000643778.1		c.1524G>T	p.Leu508Phe	missense	Exon 3 of 3	ENSP00000496428.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 64

GnomAD4 genome Cov.: 30

Alfa AF: 0.00 Hom.: 165784

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.060
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	10
DANN	Benign	0.94
DEOGEN2	Benign	0.10	T
Eigen	Benign	-0.86
Eigen_PC	Benign	-0.73
FATHMM_MKL	Benign	0.47	N
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.0058	T
MetaRNN	Benign	0.066	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.39	N
PhyloP100		0.048
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.50	N
REVEL	Benign	0.051
Sift	Benign	0.19	T
Sift4G	Benign	0.25	T
Polyphen		0.0020	B
Vest4		0.038
MutPred		0.46		Gain of sheet (P = 0.0344)
MVP		0.42
MPC		0.045
ClinPred		0.074	T
GERP RS		-1.6
Varity_R		0.056
gMVP		0.21
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs3825413; hg19: chr13-86369120;