13-85794096-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_032229.3(SLITRK6):c.2413T>C(p.Tyr805His) variant causes a missense change. The variant allele was found at a frequency of 0.000157 in 1,613,064 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Y805C) has been classified as Uncertain significance.
Frequency
Consequence
NM_032229.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLITRK6 | NM_032229.3 | c.2413T>C | p.Tyr805His | missense_variant | 2/2 | ENST00000647374.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLITRK6 | ENST00000647374.2 | c.2413T>C | p.Tyr805His | missense_variant | 2/2 | NM_032229.3 | P1 | ||
SLITRK6 | ENST00000643778.1 | c.2413T>C | p.Tyr805His | missense_variant | 3/3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000224 AC: 34AN: 151936Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000230 AC: 57AN: 247932Hom.: 0 AF XY: 0.000201 AC XY: 27AN XY: 134462
GnomAD4 exome AF: 0.000150 AC: 219AN: 1461010Hom.: 0 Cov.: 31 AF XY: 0.000154 AC XY: 112AN XY: 726824
GnomAD4 genome AF: 0.000224 AC: 34AN: 152054Hom.: 0 Cov.: 32 AF XY: 0.000229 AC XY: 17AN XY: 74340
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Apr 06, 2020 | In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Apr 21, 2023 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 1197937). This variant has not been reported in the literature in individuals affected with SLITRK6-related conditions. This variant is present in population databases (rs200882739, gnomAD 0.06%). This sequence change replaces tyrosine, which is neutral and polar, with histidine, which is basic and polar, at codon 805 of the SLITRK6 protein (p.Tyr805His). - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 16, 2021 | The c.2413T>C (p.Y805H) alteration is located in exon 2 (coding exon 1) of the SLITRK6 gene. This alteration results from a T to C substitution at nucleotide position 2413, causing the tyrosine (Y) at amino acid position 805 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
High myopia-sensorineural deafness syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Al Jalila Children’s Genomics Center, Al Jalila Childrens Speciality Hospital | Feb 11, 2020 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at