rs375015931
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_021098.3(CACNA1H):āc.5081T>Cā(p.Met1694Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000213 in 1,608,770 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. M1694V) has been classified as Uncertain significance.
Frequency
Consequence
NM_021098.3 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CACNA1H | NM_021098.3 | c.5081T>C | p.Met1694Thr | missense_variant | 29/35 | ENST00000348261.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CACNA1H | ENST00000348261.11 | c.5081T>C | p.Met1694Thr | missense_variant | 29/35 | 1 | NM_021098.3 | P4 |
Frequencies
GnomAD3 genomes AF: 0.0000920 AC: 14AN: 152232Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000417 AC: 10AN: 239896Hom.: 0 AF XY: 0.00000767 AC XY: 1AN XY: 130452
GnomAD4 exome AF: 0.000226 AC: 329AN: 1456420Hom.: 0 Cov.: 33 AF XY: 0.000222 AC XY: 161AN XY: 724014
GnomAD4 genome AF: 0.0000919 AC: 14AN: 152350Hom.: 0 Cov.: 33 AF XY: 0.0000671 AC XY: 5AN XY: 74500
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 | Jul 16, 2021 | - - |
Idiopathic generalized epilepsy;C4310756:Hyperaldosteronism, familial, type IV Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | May 09, 2023 | This variant is present in population databases (rs375015931, gnomAD 0.009%). This sequence change replaces methionine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 1694 of the CACNA1H protein (p.Met1694Thr). This variant has not been reported in the literature in individuals affected with CACNA1H-related conditions. 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 not expected to disrupt CACNA1H protein function. ClinVar contains an entry for this variant (Variation ID: 529593). - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Athena Diagnostics | Oct 30, 2017 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at