rs368421264
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP3BP6
The NM_000069.3(CACNA1S):c.4690G>A(p.Glu1564Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000229 in 1,613,114 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. E1564E) has been classified as Likely benign.
Frequency
Consequence
NM_000069.3 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 |
---|---|---|---|---|---|---|---|
CACNA1S | NM_000069.3 | c.4690G>A | p.Glu1564Lys | missense_variant | 39/44 | ENST00000362061.4 | |
CACNA1S | XM_005245478.4 | c.4633G>A | p.Glu1545Lys | missense_variant | 38/43 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CACNA1S | ENST00000362061.4 | c.4690G>A | p.Glu1564Lys | missense_variant | 39/44 | 1 | NM_000069.3 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000394 AC: 6AN: 152138Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000199 AC: 5AN: 250700Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135578
GnomAD4 exome AF: 0.0000212 AC: 31AN: 1460976Hom.: 0 Cov.: 31 AF XY: 0.0000179 AC XY: 13AN XY: 726842
GnomAD4 genome ? AF: 0.0000394 AC: 6AN: 152138Hom.: 0 Cov.: 31 AF XY: 0.0000404 AC XY: 3AN XY: 74304
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Dec 17, 2019 | 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 - |
Malignant hyperthermia, susceptibility to, 5;C3714580:Hypokalemic periodic paralysis, type 1 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 19, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at