rs966502877
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 1P and 1B. PP2BS1_Supporting
The NM_001367721.1(CASK):c.2588C>T(p.Thr863Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000503 in 1,192,756 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. T863T) has been classified as Likely benign.
Frequency
Consequence
NM_001367721.1 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CASK | NM_001367721.1 | c.2588C>T | p.Thr863Ile | missense_variant | 26/27 | ENST00000378163.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CASK | ENST00000378163.7 | c.2588C>T | p.Thr863Ile | missense_variant | 26/27 | 5 | NM_001367721.1 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000910 AC: 1AN: 109840Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0AN XY: 32204
GnomAD3 exomes AF: 0.0000226 AC: 4AN: 176655Hom.: 0 AF XY: 0.0000162 AC XY: 1AN XY: 61771
GnomAD4 exome AF: 0.00000462 AC: 5AN: 1082916Hom.: 0 Cov.: 28 AF XY: 0.00000286 AC XY: 1AN XY: 349512
GnomAD4 genome ? AF: 0.00000910 AC: 1AN: 109840Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0AN XY: 32204
ClinVar
Submissions by phenotype
Intellectual disability, CASK-related, X-linked Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 29, 2023 | This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 858 of the CASK protein (p.Thr858Ile). This variant is present in population databases (no rsID available, gnomAD 0.02%), including at least one homozygous and/or hemizygous individual. This variant has not been reported in the literature in individuals affected with CASK-related conditions. ClinVar contains an entry for this variant (Variation ID: 470210). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on CASK protein function. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at