rs183042575
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PP3_Moderate
The NM_021098.3(CACNA1H):c.2389C>T(p.Arg797Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000706 in 1,557,292 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 Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R797H) has been classified as Uncertain significance.
Frequency
Consequence
NM_021098.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CACNA1H | NM_021098.3 | c.2389C>T | p.Arg797Cys | missense_variant | 10/35 | ENST00000348261.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CACNA1H | ENST00000348261.11 | c.2389C>T | p.Arg797Cys | missense_variant | 10/35 | 1 | NM_021098.3 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152240Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000990 AC: 2AN: 202024Hom.: 0 AF XY: 0.00000925 AC XY: 1AN XY: 108058
GnomAD4 exome AF: 0.00000712 AC: 10AN: 1404934Hom.: 0 Cov.: 33 AF XY: 0.00000867 AC XY: 6AN XY: 692372
GnomAD4 genome ? AF: 0.00000656 AC: 1AN: 152358Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74502
ClinVar
Submissions by phenotype
CACNA1H-related disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Feb 14, 2024 | The CACNA1H c.2389C>T variant is predicted to result in the amino acid substitution p.Arg797Cys. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0021% of alleles in individuals of European (Non-Finnish) descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
Idiopathic generalized epilepsy;C4310756:Hyperaldosteronism, familial, type IV Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 05, 2022 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 529552). This variant has not been reported in the literature in individuals affected with CACNA1H-related conditions. This variant is present in population databases (rs183042575, gnomAD 0.002%). This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 797 of the CACNA1H protein (p.Arg797Cys). - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | May 20, 2022 | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at