X-41520464-C-T
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 1P and 5B. PP2BP4BS2
The NM_001367721.1(CASK):c.2737G>A(p.Val913Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000414 in 1,208,018 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 (★★).
Frequency
Consequence
NM_001367721.1 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CASK | NM_001367721.1 | c.2737G>A | p.Val913Met | missense_variant | Exon 27 of 27 | ENST00000378163.7 | NP_001354650.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00000896 AC: 1AN: 111560Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0AN XY: 33736
GnomAD4 exome AF: 0.00000365 AC: 4AN: 1096458Hom.: 0 Cov.: 29 AF XY: 0.00000553 AC XY: 2AN XY: 361900
GnomAD4 genome AF: 0.00000896 AC: 1AN: 111560Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0AN XY: 33736
ClinVar
Submissions by phenotype
not provided Uncertain:2
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The V908M variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The V908M variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The V908M variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. However, this substitution occurs at a position that is conserved across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at