rs367895193
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP2BP4BP6BS2
The ENST00000399655.6(CACNA1C):c.3862G>A(p.Ala1288Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000462 in 1,581,326 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A1288S) has been classified as Uncertain significance.
Frequency
Consequence
ENST00000399655.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CACNA1C | NM_000719.7 | c.3862G>A | p.Ala1288Thr | missense_variant | 30/47 | ENST00000399655.6 | NP_000710.5 | |
CACNA1C | NM_001167623.2 | c.3912+618G>A | intron_variant | ENST00000399603.6 | NP_001161095.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CACNA1C | ENST00000399655.6 | c.3862G>A | p.Ala1288Thr | missense_variant | 30/47 | 1 | NM_000719.7 | ENSP00000382563 | ||
CACNA1C | ENST00000399603.6 | c.3912+618G>A | intron_variant | 5 | NM_001167623.2 | ENSP00000382512 |
Frequencies
GnomAD3 genomes AF: 0.0000265 AC: 4AN: 150724Hom.: 0 Cov.: 29
GnomAD3 exomes AF: 0.0000817 AC: 17AN: 207986Hom.: 0 AF XY: 0.0000539 AC XY: 6AN XY: 111214
GnomAD4 exome AF: 0.0000482 AC: 69AN: 1430602Hom.: 0 Cov.: 29 AF XY: 0.0000466 AC XY: 33AN XY: 708658
GnomAD4 genome AF: 0.0000265 AC: 4AN: 150724Hom.: 0 Cov.: 29 AF XY: 0.0000272 AC XY: 2AN XY: 73486
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Aug 30, 2023 | Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant does not alter protein structure/function - |
Long QT syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 11, 2024 | - - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | May 27, 2022 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at