chr1-181763493-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PP2PP3PP5
The NM_001205293.3(CACNA1E):āc.4777A>Gā(p.Ile1593Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000125 in 1,595,668 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 Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_001205293.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CACNA1E | NM_001205293.3 | c.4777A>G | p.Ile1593Val | missense_variant | 34/48 | ENST00000367573.7 | NP_001192222.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CACNA1E | ENST00000367573.7 | c.4777A>G | p.Ile1593Val | missense_variant | 34/48 | 1 | NM_001205293.3 | ENSP00000356545.2 | ||
CACNA1E | ENST00000360108.7 | c.4720A>G | p.Ile1574Val | missense_variant | 33/47 | 5 | ENSP00000353222.3 | |||
CACNA1E | ENST00000367570.6 | c.4777A>G | p.Ile1593Val | missense_variant | 34/47 | 1 | ENSP00000356542.1 | |||
CACNA1E | ENST00000621791.4 | c.4720A>G | p.Ile1574Val | missense_variant | 33/46 | 1 | ENSP00000481619.1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152158Hom.: 0 Cov.: 32
GnomAD4 exome AF: 6.93e-7 AC: 1AN: 1443510Hom.: 0 Cov.: 30 AF XY: 0.00000140 AC XY: 1AN XY: 715196
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152158Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74340
ClinVar
Submissions by phenotype
not provided Pathogenic:1Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing;provider interpretation | Geisinger Autism and Developmental Medicine Institute, Geisinger Health System | Mar 12, 2018 | This variant was identified in a 2 year old male with autism spectrum disorder, developmental delays, seizures, and wide-based gait. This variant is absent from the gnomAD database and computational models predict it to be damaging. The CACNA1E gene has yet to be clearly associated with a human disorder through multiple publications, although it has been suggested as a candidate gene for neurodevelopmental phenotypes (O'Roak, 2012; Helbig, 2016). It is also constrained for both missense and loss of function variation based on population data. The laboratory report indicates additional internal data which implicates this gene as causative for neurodevelopmental phenotypes; however, this is not yet publicly available. Therefore, although this is a highly suspicious variant, we consider this a variant of uncertain significance at this time. - |
Likely pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Nov 30, 2023 | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 30311381) - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at