1-181721870-G-T
Variant summary
Our verdict is Pathogenic. Variant got 13 ACMG points: 13P and 0B. PM1PM2PM5PP2PP3_StrongPP5_Moderate
The NM_001205293.3(CACNA1E):c.2069G>T(p.Gly690Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G690D) has been classified as Uncertain significance.
Frequency
Consequence
NM_001205293.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CACNA1E | NM_001205293.3 | c.2069G>T | p.Gly690Val | missense_variant | 16/48 | ENST00000367573.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CACNA1E | ENST00000367573.7 | c.2069G>T | p.Gly690Val | missense_variant | 16/48 | 1 | NM_001205293.3 | A2 | |
CACNA1E | ENST00000367570.6 | c.2069G>T | p.Gly690Val | missense_variant | 16/47 | 1 | P4 | ||
CACNA1E | ENST00000621791.4 | c.2069G>T | p.Gly690Val | missense_variant | 16/46 | 1 | A2 | ||
CACNA1E | ENST00000360108.7 | c.2069G>T | p.Gly690Val | missense_variant | 16/47 | 5 | A2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome Cov.: 27
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
not provided Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Invitae | Dec 28, 2020 | 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 CACNA1E protein function. This variant has not been reported in the literature in individuals with CACNA1E-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces glycine with valine at codon 690 of the CACNA1E protein (p.Gly690Val). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and valine. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the p.Gly690 amino acid residue in CACNA1E. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 30343943). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.