16-1207426-C-A
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3BS2
The NM_021098.3(CACNA1H):c.3059C>A(p.Ala1020Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00000434 in 1,612,346 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. A1020V) has been classified as Uncertain significance.
Frequency
Consequence
NM_021098.3 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 |
---|---|---|---|---|---|---|---|
CACNA1H | NM_021098.3 | c.3059C>A | p.Ala1020Glu | missense_variant | 14/35 | ENST00000348261.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CACNA1H | ENST00000348261.11 | c.3059C>A | p.Ala1020Glu | missense_variant | 14/35 | 1 | NM_021098.3 | P4 |
Frequencies
GnomAD3 genomes AF: 0.00000659 AC: 1AN: 151772Hom.: 0 Cov.: 30
GnomAD3 exomes AF: 0.00000405 AC: 1AN: 247050Hom.: 0 AF XY: 0.00000743 AC XY: 1AN XY: 134632
GnomAD4 exome AF: 0.00000411 AC: 6AN: 1460574Hom.: 0 Cov.: 33 AF XY: 0.00000551 AC XY: 4AN XY: 726566
GnomAD4 genome AF: 0.00000659 AC: 1AN: 151772Hom.: 0 Cov.: 30 AF XY: 0.0000135 AC XY: 1AN XY: 74120
ClinVar
Submissions by phenotype
Idiopathic generalized epilepsy;C4310756:Hyperaldosteronism, familial, type IV Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Feb 09, 2022 | This variant has not been reported in the literature in individuals affected with CACNA1H-related conditions. 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 529558). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This sequence change replaces alanine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 1020 of the CACNA1H protein (p.Ala1020Glu). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at