rs1131691712
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_001127222.2(CACNA1A):c.3103dupT(p.Ser1035PhefsTer32) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_001127222.2 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CACNA1A | ENST00000360228.11 | c.3103dupT | p.Ser1035PhefsTer32 | frameshift_variant | Exon 20 of 47 | 1 | NM_001127222.2 | ENSP00000353362.5 | ||
CACNA1A | ENST00000638029.1 | c.3115dupT | p.Ser1039PhefsTer32 | frameshift_variant | Exon 20 of 48 | 5 | ENSP00000489829.1 | |||
CACNA1A | ENST00000573710.7 | c.3109dupT | p.Ser1037PhefsTer32 | frameshift_variant | Exon 20 of 47 | 5 | ENSP00000460092.3 | |||
CACNA1A | ENST00000635727.1 | c.3106dupT | p.Ser1036PhefsTer32 | frameshift_variant | Exon 20 of 47 | 5 | ENSP00000490001.1 | |||
CACNA1A | ENST00000637769.1 | c.3106dupT | p.Ser1036PhefsTer32 | frameshift_variant | Exon 20 of 47 | 1 | ENSP00000489778.1 | |||
CACNA1A | ENST00000636012.1 | c.3106dupT | p.Ser1036PhefsTer32 | frameshift_variant | Exon 20 of 46 | 5 | ENSP00000490223.1 | |||
CACNA1A | ENST00000637736.1 | c.2965dupT | p.Ser989PhefsTer32 | frameshift_variant | Exon 19 of 46 | 5 | ENSP00000489861.1 | |||
CACNA1A | ENST00000636389.1 | c.3106dupT | p.Ser1036PhefsTer32 | frameshift_variant | Exon 20 of 47 | 5 | ENSP00000489992.1 | |||
CACNA1A | ENST00000637432.1 | c.3115dupT | p.Ser1039PhefsTer32 | frameshift_variant | Exon 20 of 48 | 5 | ENSP00000490617.1 | |||
CACNA1A | ENST00000636549.1 | c.3106dupT | p.Ser1036PhefsTer32 | frameshift_variant | Exon 20 of 48 | 5 | ENSP00000490578.1 | |||
CACNA1A | ENST00000637927.1 | c.3109dupT | p.Ser1037PhefsTer32 | frameshift_variant | Exon 20 of 47 | 5 | ENSP00000489715.1 | |||
CACNA1A | ENST00000635895.1 | c.3106dupT | p.Ser1036PhefsTer32 | frameshift_variant | Exon 20 of 47 | 5 | ENSP00000490323.1 | |||
CACNA1A | ENST00000638009.2 | c.3106dupT | p.Ser1036PhefsTer32 | frameshift_variant | Exon 20 of 47 | 1 | ENSP00000489913.1 | |||
CACNA1A | ENST00000637276.1 | c.3106dupT | p.Ser1036PhefsTer32 | frameshift_variant | Exon 20 of 46 | 5 | ENSP00000489777.1 |
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD4 exome Cov.: 35
GnomAD4 genome Cov.: 31
ClinVar
Submissions by phenotype
Inborn genetic diseases Pathogenic:1
- -
not provided Pathogenic:1
The c.3106dupT variant in the CACNA1A gene has not been reported previously as a pathogenicvariant nor as a benign variant, to our knowledge. The c.3106dupT variant causes a frameshift startingwith codon Serine 1036, changes this amino acid to a Phenylalanine residue, and creates a prematureStop codon at position 32 of the new reading frame, denoted p.Ser1036PhefsX32. This variant ispredicted to cause loss of normal protein function either through protein truncation or nonsensemediatedmRNA decay. The c.3106dupT variant is not observed in large population cohorts (Lek etal., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). We interpret c.3106dupTas a pathogenic variant. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at