16-1207426-C-T
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3BS2
The NM_021098.3(CACNA1H):c.3059C>T(p.Ala1020Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000174 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>T | p.Ala1020Val | missense_variant | Exon 14 of 35 | 1 | NM_021098.3 | ENSP00000334198.7 | ||
CACNA1H | ENST00000565831.6 | c.3059C>T | p.Ala1020Val | missense_variant | Exon 13 of 33 | 1 | ENSP00000455840.1 | |||
CACNA1H | ENST00000638323.1 | c.3020C>T | p.Ala1007Val | missense_variant | Exon 14 of 35 | 5 | ENSP00000492267.1 | |||
CACNA1H | ENST00000639478.1 | n.3059C>T | non_coding_transcript_exon_variant | Exon 14 of 35 | 5 | ENSP00000491945.1 | ||||
CACNA1H | ENST00000640028.1 | n.*972C>T | non_coding_transcript_exon_variant | Exon 14 of 35 | 5 | ENSP00000491488.1 | ||||
CACNA1H | ENST00000640028.1 | n.*972C>T | 3_prime_UTR_variant | Exon 14 of 35 | 5 | ENSP00000491488.1 |
Frequencies
GnomAD3 genomes AF: 0.0000132 AC: 2AN: 151772Hom.: 0 Cov.: 30
GnomAD3 exomes AF: 0.0000243 AC: 6AN: 247050Hom.: 0 AF XY: 0.0000297 AC XY: 4AN XY: 134632
GnomAD4 exome AF: 0.0000178 AC: 26AN: 1460574Hom.: 0 Cov.: 33 AF XY: 0.0000248 AC XY: 18AN XY: 726566
GnomAD4 genome AF: 0.0000132 AC: 2AN: 151772Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN 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
This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1020 of the CACNA1H protein (p.Ala1020Val). This variant is present in population databases (rs771994752, gnomAD 0.009%). This variant has not been reported in the literature in individuals affected with CACNA1H-related conditions. ClinVar contains an entry for this variant (Variation ID: 2026123). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on CACNA1H protein function. 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