rs775971172
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.
The NM_021098.3(CACNA1H):c.4070A>T(p.His1357Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000131 in 1,602,944 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. H1357H) has been classified as Likely benign.
Frequency
Consequence
NM_021098.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CACNA1H | NM_021098.3 | c.4070A>T | p.His1357Leu | missense_variant | 21/35 | ENST00000348261.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CACNA1H | ENST00000348261.11 | c.4070A>T | p.His1357Leu | missense_variant | 21/35 | 1 | NM_021098.3 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152242Hom.: 0 Cov.: 35
GnomAD3 exomes AF: 0.0000125 AC: 3AN: 240472Hom.: 0 AF XY: 0.00000759 AC XY: 1AN XY: 131712
GnomAD4 exome AF: 0.0000117 AC: 17AN: 1450702Hom.: 0 Cov.: 39 AF XY: 0.0000111 AC XY: 8AN XY: 722190
GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152242Hom.: 0 Cov.: 35 AF XY: 0.0000269 AC XY: 2AN XY: 74378
ClinVar
Submissions by phenotype
Idiopathic generalized epilepsy;C4310756:Hyperaldosteronism, familial, type IV Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 23, 2021 | This sequence change replaces histidine with leucine at codon 1357 of the CACNA1H protein (p.His1357Leu). The histidine residue is weakly conserved and there is a moderate physicochemical difference between histidine and leucine. This variant is present in population databases (rs775971172, ExAC 0.002%). This variant has not been reported in the literature in individuals with CACNA1H-related disease. ClinVar contains an entry for this variant (Variation ID: 529589). 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: "Benign"; Align-GVGD: "Class C0"). 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