rs900079494
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP2BP4_ModerateBS2
The NM_001367721.1(CASK):c.1717A>T(p.Thr573Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000331 in 1,208,576 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 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. T573I) has been classified as Likely benign.
Frequency
Consequence
NM_001367721.1 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CASK | NM_001367721.1 | c.1717A>T | p.Thr573Ser | missense_variant | 18/27 | ENST00000378163.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CASK | ENST00000378163.7 | c.1717A>T | p.Thr573Ser | missense_variant | 18/27 | 5 | NM_001367721.1 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000892 AC: 1AN: 112048Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0AN XY: 34236
GnomAD4 exome AF: 0.00000274 AC: 3AN: 1096528Hom.: 0 Cov.: 28 AF XY: 0.00000553 AC XY: 2AN XY: 361930
GnomAD4 genome ? AF: 0.00000892 AC: 1AN: 112048Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0AN XY: 34236
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 03, 2017 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Aug 19, 2016 | - - |
Intellectual disability, CASK-related, X-linked Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 05, 2023 | This sequence change replaces threonine, which is neutral and polar, with serine, which is neutral and polar, at codon 573 of the CASK protein (p.Thr573Ser). 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. 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. ClinVar contains an entry for this variant (Variation ID: 376867). This variant has not been reported in the literature in individuals affected with CASK-related conditions. This variant is not present in population databases (gnomAD no frequency). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at