NM_032229.3:c.2382C>A

Variant names:

• chr13-85794127-G-T
• NM_032229.3:c.2382C>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_032229.3(SLITRK6):​c.2382C>A​(p.His794Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,022 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict 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: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SLITRK6 NM_032229.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.704

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03836608).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLITRK6	NM_032229.3	c.2382C>A	p.His794Gln	missense_variant	Exon 2 of 2	ENST00000647374.2	NP_115605.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLITRK6	ENST00000647374.2	c.2382C>A	p.His794Gln	missense_variant	Exon 2 of 2		NM_032229.3	ENSP00000495507.1
SLITRK6	ENST00000643778.1	c.2382C>A	p.His794Gln	missense_variant	Exon 3 of 3			ENSP00000496428.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461022 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726824

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	0.0010
DANN	Benign	0.58
DEOGEN2	Benign	0.079	T;T;T
Eigen	Benign	-1.9
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.60	.;.;T
M_CAP	Benign	0.0058	T
MetaRNN	Benign	0.038	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L;L;L
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	0.15	.;N;.
REVEL	Benign	0.072
Sift	Benign	0.79	.;T;.
Sift4G	Benign	1.0	.;T;.
Polyphen		0.0	B;B;B
Vest4		0.14
MutPred		0.20		Loss of ubiquitination at K798 (P = 0.1083);Loss of ubiquitination at K798 (P = 0.1083);Loss of ubiquitination at K798 (P = 0.1083);
MVP		0.36
MPC		0.042
ClinPred		0.048	T
GERP RS		-12
Varity_R		0.044
gMVP		0.28

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr13-86368262;