rs777945001
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 3P and 5B. PP2PP3_ModerateBP6BS2
The NM_000719.7(CACNA1C):c.1693G>A(p.Ala565Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000182 in 1,596,520 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). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A565S) has been classified as Uncertain significance.
Frequency
Consequence
NM_000719.7 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 |
---|---|---|---|---|---|---|---|
CACNA1C | NM_000719.7 | c.1693G>A | p.Ala565Thr | missense_variant | 13/47 | ENST00000399655.6 | |
CACNA1C | NM_001167623.2 | c.1693G>A | p.Ala565Thr | missense_variant | 13/47 | ENST00000399603.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CACNA1C | ENST00000399603.6 | c.1693G>A | p.Ala565Thr | missense_variant | 13/47 | 5 | NM_001167623.2 | ||
CACNA1C | ENST00000399655.6 | c.1693G>A | p.Ala565Thr | missense_variant | 13/47 | 1 | NM_000719.7 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152136Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000318 AC: 7AN: 220120Hom.: 0 AF XY: 0.0000589 AC XY: 7AN XY: 118822
GnomAD4 exome AF: 0.0000187 AC: 27AN: 1444266Hom.: 0 Cov.: 31 AF XY: 0.0000293 AC XY: 21AN XY: 716664
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152254Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74454
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | May 31, 2023 | Has not been previously published as pathogenic or benign in association with a CACNA1C-related disorder to our knowledge; In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 34436362) - |
Long QT syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jul 17, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at