rs187259531
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 3P and 7B. PM1PP2BP4_ModerateBS1_SupportingBS2
The NM_001127222.2(CACNA1A):c.1225A>C(p.Thr409Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000155 in 1,612,972 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_001127222.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CACNA1A | NM_001127222.2 | c.1225A>C | p.Thr409Pro | missense_variant | 9/47 | ENST00000360228.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CACNA1A | ENST00000360228.11 | c.1225A>C | p.Thr409Pro | missense_variant | 9/47 | 1 | NM_001127222.2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000789 AC: 12AN: 152086Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.00000403 AC: 1AN: 248274Hom.: 0 AF XY: 0.00000742 AC XY: 1AN XY: 134710
GnomAD4 exome AF: 0.00000890 AC: 13AN: 1460768Hom.: 0 Cov.: 29 AF XY: 0.00000826 AC XY: 6AN XY: 726698
GnomAD4 genome ? AF: 0.0000788 AC: 12AN: 152204Hom.: 0 Cov.: 31 AF XY: 0.0000672 AC XY: 5AN XY: 74422
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Nov 16, 2023 | Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant has a deleterious effect on protein structure/function - |
Uncertain significance, criteria provided, single submitter | clinical testing | Athena Diagnostics | Aug 16, 2019 | - - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 12, 2024 | The c.1225A>C (p.T409P) alteration is located in exon 9 (coding exon 9) of the CACNA1A gene. This alteration results from a A to C substitution at nucleotide position 1225, causing the threonine (T) at amino acid position 409 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Episodic ataxia type 2;C4310716:Developmental and epileptic encephalopathy, 42 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 15, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at