rs147112322
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6
The NM_000069.3(CACNA1S):c.2099C>T(p.Thr700Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00023 in 1,614,156 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign 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. T700T) has been classified as Likely benign.
Frequency
Consequence
NM_000069.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CACNA1S | NM_000069.3 | c.2099C>T | p.Thr700Met | missense_variant | 15/44 | ENST00000362061.4 | |
CACNA1S | XM_005245478.4 | c.2099C>T | p.Thr700Met | missense_variant | 15/43 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CACNA1S | ENST00000362061.4 | c.2099C>T | p.Thr700Met | missense_variant | 15/44 | 1 | NM_000069.3 | P2 |
Frequencies
GnomAD3 genomes AF: 0.000151 AC: 23AN: 152188Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000191 AC: 48AN: 251488Hom.: 0 AF XY: 0.000184 AC XY: 25AN XY: 135920
GnomAD4 exome AF: 0.000238 AC: 348AN: 1461850Hom.: 1 Cov.: 32 AF XY: 0.000237 AC XY: 172AN XY: 727236
GnomAD4 genome AF: 0.000151 AC: 23AN: 152306Hom.: 0 Cov.: 33 AF XY: 0.000134 AC XY: 10AN XY: 74486
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jul 01, 2024 | CACNA1S: PM2:Supporting, BP4 - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Sep 25, 2023 | Reported previously in an individual with susceptibility to malignant hyperthermia who also harbored another CACNA1S variant, as well as a variant in RYR1 (Gillies et al., 2015); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 25735680) - |
Malignant hyperthermia, susceptibility to, 5 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Institute of Human Genetics, University of Leipzig Medical Center | Aug 03, 2021 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Apr 17, 2020 | - - |
Malignant hyperthermia, susceptibility to, 5;C3714580:Hypokalemic periodic paralysis, type 1 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 12, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at