rs530655602
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 1P and 7B. PP3BP4_ModerateBP6BS1
The NM_000069.3(CACNA1S):c.3761G>A(p.Arg1254Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000305 in 1,614,140 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts 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. R1254G) has been classified as Uncertain significance.
Frequency
Consequence
NM_000069.3 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CACNA1S | NM_000069.3 | c.3761G>A | p.Arg1254Gln | missense_variant | 30/44 | ENST00000362061.4 | |
CACNA1S | XM_005245478.4 | c.3704G>A | p.Arg1235Gln | missense_variant | 29/43 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CACNA1S | ENST00000362061.4 | c.3761G>A | p.Arg1254Gln | missense_variant | 30/44 | 1 | NM_000069.3 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.000197 AC: 30AN: 152142Hom.: 1 Cov.: 32
GnomAD3 exomes AF: 0.000660 AC: 166AN: 251398Hom.: 1 AF XY: 0.000765 AC XY: 104AN XY: 135876
GnomAD4 exome AF: 0.000316 AC: 462AN: 1461880Hom.: 4 Cov.: 35 AF XY: 0.000421 AC XY: 306AN XY: 727244
GnomAD4 genome ? AF: 0.000197 AC: 30AN: 152260Hom.: 1 Cov.: 32 AF XY: 0.000255 AC XY: 19AN XY: 74446
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Apr 01, 2018 | - - |
CACNA1S-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Mar 10, 2020 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Malignant hyperthermia, susceptibility to, 5;C3714580:Hypokalemic periodic paralysis, type 1 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at