rs775079932
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 1P and 7B. PP2BP4_ModerateBP6BS2
The ENST00000360228.11(CACNA1A):c.3175C>T(p.Pro1059Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000483 in 1,613,540 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict 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. P1059T) has been classified as Uncertain significance.
Frequency
Consequence
ENST00000360228.11 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CACNA1A | NM_001127222.2 | c.3175C>T | p.Pro1059Ser | missense_variant | 20/47 | ENST00000360228.11 | NP_001120694.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CACNA1A | ENST00000360228.11 | c.3175C>T | p.Pro1059Ser | missense_variant | 20/47 | 1 | NM_001127222.2 | ENSP00000353362 |
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152220Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000447 AC: 11AN: 246036Hom.: 0 AF XY: 0.0000373 AC XY: 5AN XY: 134204
GnomAD4 exome AF: 0.0000493 AC: 72AN: 1461320Hom.: 0 Cov.: 35 AF XY: 0.0000509 AC XY: 37AN XY: 726952
GnomAD4 genome AF: 0.0000394 AC: 6AN: 152220Hom.: 0 Cov.: 31 AF XY: 0.0000403 AC XY: 3AN XY: 74366
ClinVar
Submissions by phenotype
not provided Uncertain:2Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Apr 02, 2020 | This variant is associated with the following publications: (PMID: 31731261) - |
Uncertain significance, criteria provided, single submitter | clinical testing | Athena Diagnostics | Dec 30, 2017 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Nov 01, 2023 | - - |
Episodic ataxia type 2;C4310716:Developmental and epileptic encephalopathy, 42 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Nov 18, 2023 | - - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | May 04, 2019 | 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