rs771994752
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 (★★).
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
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CACNA1H | ENST00000348261.11 | c.3059C>A | p.Ala1020Glu | missense_variant | Exon 14 of 35 | 1 | NM_021098.3 | ENSP00000334198.7 | ||
CACNA1H | ENST00000565831.6 | c.3059C>A | p.Ala1020Glu | missense_variant | Exon 13 of 33 | 1 | ENSP00000455840.1 | |||
CACNA1H | ENST00000638323.1 | c.3020C>A | p.Ala1007Glu | missense_variant | Exon 14 of 35 | 5 | ENSP00000492267.1 | |||
CACNA1H | ENST00000639478.1 | n.3059C>A | non_coding_transcript_exon_variant | Exon 14 of 35 | 5 | ENSP00000491945.1 | ||||
CACNA1H | ENST00000640028.1 | n.*972C>A | non_coding_transcript_exon_variant | Exon 14 of 35 | 5 | ENSP00000491488.1 | ||||
CACNA1H | ENST00000640028.1 | n.*972C>A | 3_prime_UTR_variant | Exon 14 of 35 | 5 | ENSP00000491488.1 |
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
Epilepsy, childhood absence, susceptibility to, 6;C4310756:Hyperaldosteronism, familial, type IV Uncertain:1
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Idiopathic generalized epilepsy;C4310756:Hyperaldosteronism, familial, type IV Uncertain:1
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 has not been reported in the literature in individuals affected with CACNA1H-related conditions. 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). 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. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at