rs1555825315
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM1PM2PP2
The NM_000719.7(CACNA1C):āc.1951A>Gā(p.Ile651Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000691 in 1,446,922 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I651N) has been classified as Uncertain significance.
Frequency
Consequence
NM_000719.7 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 | UniProt |
---|---|---|---|---|---|---|---|
CACNA1C | NM_000719.7 | c.1951A>G | p.Ile651Val | missense_variant | 14/47 | ENST00000399655.6 | |
CACNA1C | NM_001167623.2 | c.1951A>G | p.Ile651Val | missense_variant | 14/47 | ENST00000399603.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CACNA1C | ENST00000399603.6 | c.1951A>G | p.Ile651Val | missense_variant | 14/47 | 5 | NM_001167623.2 | ||
CACNA1C | ENST00000399655.6 | c.1951A>G | p.Ile651Val | missense_variant | 14/47 | 1 | NM_000719.7 |
Frequencies
GnomAD3 genomes ? Cov.: 29
GnomAD4 exome AF: 6.91e-7 AC: 1AN: 1446922Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 717996
GnomAD4 genome ? Cov.: 29
ClinVar
Submissions by phenotype
Long QT syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 02, 2018 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with CACNA1C-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces isoleucine with valine at codon 651 of the CACNA1C protein (p.Ile651Val). The isoleucine residue is highly conserved and there is a small physicochemical difference between isoleucine and valine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at