rs1555515661
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_021098.3(CACNA1H):c.3599A>C(p.Asp1200Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000714 in 1,400,314 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_021098.3 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CACNA1H | ENST00000348261.11 | c.3599A>C | p.Asp1200Ala | missense_variant | Exon 17 of 35 | 1 | NM_021098.3 | ENSP00000334198.7 | ||
CACNA1H | ENST00000565831.6 | c.3599A>C | p.Asp1200Ala | missense_variant | Exon 16 of 33 | 1 | ENSP00000455840.1 | |||
CACNA1H | ENST00000638323.1 | c.3560A>C | p.Asp1187Ala | missense_variant | Exon 17 of 35 | 5 | ENSP00000492267.1 | |||
CACNA1H | ENST00000639478.1 | n.3599A>C | non_coding_transcript_exon_variant | Exon 17 of 35 | 5 | ENSP00000491945.1 | ||||
CACNA1H | ENST00000640028.1 | n.*1512A>C | non_coding_transcript_exon_variant | Exon 17 of 35 | 5 | ENSP00000491488.1 | ||||
CACNA1H | ENST00000640028.1 | n.*1512A>C | 3_prime_UTR_variant | Exon 17 of 35 | 5 | ENSP00000491488.1 | ||||
CACNA1H | ENST00000637236.2 | n.-89A>C | upstream_gene_variant | 5 | ENSP00000492650.2 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome AF: 7.14e-7 AC: 1AN: 1400314Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 692546
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Epilepsy, childhood absence, susceptibility to, 6 Uncertain:1
This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. -
Idiopathic generalized epilepsy;C4310756:Hyperaldosteronism, familial, type IV Uncertain:1
This sequence change replaces aspartic acid with alanine at codon 1200 of the CACNA1H protein (p.Asp1200Ala). The aspartic acid residue is moderately conserved and there is a moderate physicochemical difference between aspartic acid and alanine. While this variant is not present in population databases, the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in individuals with CACNA1H-related disease. 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 tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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