rs149658326
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP6
The NM_000069.3(CACNA1S):c.3013A>T(p.Met1005Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000116 in 1,614,060 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign 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. M1005K) has been classified as Uncertain significance.
Frequency
Consequence
NM_000069.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CACNA1S | NM_000069.3 | c.3013A>T | p.Met1005Leu | missense_variant | 24/44 | ENST00000362061.4 | |
CACNA1S | XM_005245478.4 | c.3013A>T | p.Met1005Leu | missense_variant | 24/43 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CACNA1S | ENST00000362061.4 | c.3013A>T | p.Met1005Leu | missense_variant | 24/44 | 1 | NM_000069.3 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000329 AC: 5AN: 152188Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000239 AC: 6AN: 251390Hom.: 0 AF XY: 0.0000294 AC XY: 4AN XY: 135894
GnomAD4 exome AF: 0.000125 AC: 183AN: 1461872Hom.: 0 Cov.: 33 AF XY: 0.000127 AC XY: 92AN XY: 727234
GnomAD4 genome ? AF: 0.0000329 AC: 5AN: 152188Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74356
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 | May 06, 2022 | - - |
CACNA1S-related condition Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Feb 12, 2024 | The CACNA1S c.3013A>T variant is predicted to result in the amino acid substitution p.Met1005Leu. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0062% of alleles in individuals of African descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
Malignant hyperthermia, susceptibility to, 5;C3714580:Hypokalemic periodic paralysis, type 1 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Nov 24, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at