chr16-1210811-G-A
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PP3_ModerateBS2
The NM_021098.3(CACNA1H):c.4063G>A(p.Gly1355Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000193 in 1,602,238 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 (★★). Synonymous variant affecting the same amino acid position (i.e. G1355G) has been classified as Likely benign.
Frequency
Consequence
NM_021098.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CACNA1H | NM_021098.3 | c.4063G>A | p.Gly1355Ser | missense_variant | 21/35 | ENST00000348261.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CACNA1H | ENST00000348261.11 | c.4063G>A | p.Gly1355Ser | missense_variant | 21/35 | 1 | NM_021098.3 | P4 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152252Hom.: 0 Cov.: 35
GnomAD3 exomes AF: 0.0000292 AC: 7AN: 239554Hom.: 0 AF XY: 0.0000381 AC XY: 5AN XY: 131280
GnomAD4 exome AF: 0.0000200 AC: 29AN: 1449986Hom.: 0 Cov.: 39 AF XY: 0.0000222 AC XY: 16AN XY: 721874
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152252Hom.: 0 Cov.: 35 AF XY: 0.0000269 AC XY: 2AN XY: 74390
ClinVar
Submissions by phenotype
Epilepsy, childhood absence, susceptibility to, 6;C4310756:Hyperaldosteronism, familial, type IV Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Apr 24, 2022 | - - |
Idiopathic generalized epilepsy;C4310756:Hyperaldosteronism, familial, type IV Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 12, 2022 | 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) performed at Invitae indicates that this missense variant is expected to disrupt CACNA1H protein function. ClinVar contains an entry for this variant (Variation ID: 579864). This variant has not been reported in the literature in individuals affected with CACNA1H-related conditions. This variant is present in population databases (rs747715176, gnomAD 0.01%). This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 1355 of the CACNA1H protein (p.Gly1355Ser). 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