1-201039859-TG-T
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PVS1_ModeratePM2BS1_Supporting
The NM_000069.3(CACNA1S):βc.5593delCβ(p.Gln1865ArgfsTer19) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000046 in 1,608,850 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (β β ).
Frequency
Consequence
NM_000069.3 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CACNA1S | NM_000069.3 | c.5593delC | p.Gln1865ArgfsTer19 | frameshift_variant | Exon 44 of 44 | ENST00000362061.4 | NP_000060.2 | |
CACNA1S | XM_005245478.4 | c.5536delC | p.Gln1846ArgfsTer19 | frameshift_variant | Exon 43 of 43 | XP_005245535.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000289 AC: 44AN: 152242Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.0000646 AC: 16AN: 247648Hom.: 0 AF XY: 0.0000373 AC XY: 5AN XY: 134218
GnomAD4 exome AF: 0.0000206 AC: 30AN: 1456490Hom.: 0 Cov.: 31 AF XY: 0.0000207 AC XY: 15AN XY: 724858
GnomAD4 genome AF: 0.000289 AC: 44AN: 152360Hom.: 0 Cov.: 34 AF XY: 0.000215 AC XY: 16AN XY: 74512
ClinVar
Submissions by phenotype
not provided Uncertain:1
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Malignant hyperthermia, susceptibility to, 5;C3714580:Hypokalemic periodic paralysis, type 1 Uncertain:1
This sequence change results in a frameshift in the CACNA1S gene (p.Gln1865Argfs*19). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 9 amino acid(s) of the CACNA1S protein and extend the protein by 9 additional amino acid residues. This variant is present in population databases (rs139276856, gnomAD 0.08%). This variant has not been reported in the literature in individuals affected with CACNA1S-related conditions. ClinVar contains an entry for this variant (Variation ID: 853874). 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