chr1-201076966-C-A
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM2PP3_ModerateBP6
The NM_000069.3(CACNA1S):c.1781G>T(p.Arg594Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,614,098 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). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R594C) has been classified as Benign.
Frequency
Consequence
NM_000069.3 missense
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/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CACNA1S | NM_000069.3 | c.1781G>T | p.Arg594Leu | missense_variant | 12/44 | ENST00000362061.4 | |
CACNA1S | XM_005245478.4 | c.1781G>T | p.Arg594Leu | missense_variant | 12/43 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CACNA1S | ENST00000362061.4 | c.1781G>T | p.Arg594Leu | missense_variant | 12/44 | 1 | NM_000069.3 | P2 |
Frequencies
GnomAD3 genomes AF: 0.0000854 AC: 13AN: 152204Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251494Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135922
GnomAD4 exome AF: 0.00000547 AC: 8AN: 1461894Hom.: 0 Cov.: 32 AF XY: 0.00000550 AC XY: 4AN XY: 727248
GnomAD4 genome AF: 0.0000854 AC: 13AN: 152204Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3AN XY: 74352
ClinVar
Submissions by phenotype
Malignant hyperthermia, susceptibility to, 5;C2749982:Thyrotoxic periodic paralysis, susceptibility to, 1;C3714580:Hypokalemic periodic paralysis, type 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Feb 11, 2022 | - - |
Malignant hyperthermia, susceptibility to, 5;C3714580:Hypokalemic periodic paralysis, type 1 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Mar 16, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at