chr16-1205127-C-G
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PP3_ModerateBS2
The NM_021098.3(CACNA1H):āc.2465C>Gā(p.Thr822Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000161 in 1,612,142 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 (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T822I) has been classified 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 -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CACNA1H | NM_021098.3 | c.2465C>G | p.Thr822Ser | missense_variant | 11/35 | ENST00000348261.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CACNA1H | ENST00000348261.11 | c.2465C>G | p.Thr822Ser | missense_variant | 11/35 | 1 | NM_021098.3 | P4 |
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152210Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000202 AC: 5AN: 247334Hom.: 0 AF XY: 0.00000743 AC XY: 1AN XY: 134674
GnomAD4 exome AF: 0.0000137 AC: 20AN: 1459932Hom.: 0 Cov.: 32 AF XY: 0.0000151 AC XY: 11AN XY: 726278
GnomAD4 genome AF: 0.0000394 AC: 6AN: 152210Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74358
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 | Jan 10, 2022 | - - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 22, 2023 | The c.2465C>G (p.T822S) alteration is located in exon 11 (coding exon 10) of the CACNA1H gene. This alteration results from a C to G substitution at nucleotide position 2465, causing the threonine (T) at amino acid position 822 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Idiopathic generalized epilepsy;C4310756:Hyperaldosteronism, familial, type IV Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Mar 27, 2023 | 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. 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: 807340). This variant has not been reported in the literature in individuals affected with CACNA1H-related conditions. This variant is present in population databases (rs369356684, gnomAD 0.006%). This sequence change replaces threonine, which is neutral and polar, with serine, which is neutral and polar, at codon 822 of the CACNA1H protein (p.Thr822Ser). - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jun 01, 2016 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at