chr12-2115239-G-T
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 1P and 5B. PP2BP6BS2
The NM_000719.7(CACNA1C):c.65G>T(p.Ser22Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000007 in 1,572,518 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. S22N) 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 -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CACNA1C | NM_000719.7 | c.65G>T | p.Ser22Ile | missense_variant | 2/47 | ENST00000399655.6 | |
CACNA1C | NM_001167623.2 | c.65G>T | p.Ser22Ile | missense_variant | 2/47 | ENST00000399603.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CACNA1C | ENST00000399603.6 | c.65G>T | p.Ser22Ile | missense_variant | 2/47 | 5 | NM_001167623.2 | ||
CACNA1C | ENST00000399655.6 | c.65G>T | p.Ser22Ile | missense_variant | 2/47 | 1 | NM_000719.7 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152242Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.0000295 AC: 6AN: 203076Hom.: 0 AF XY: 0.00000911 AC XY: 1AN XY: 109748
GnomAD4 exome AF: 0.00000563 AC: 8AN: 1420276Hom.: 0 Cov.: 31 AF XY: 0.00000143 AC XY: 1AN XY: 701308
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152242Hom.: 0 Cov.: 34 AF XY: 0.0000403 AC XY: 3AN XY: 74372
ClinVar
Submissions by phenotype
Timothy syndrome;C2678478:Brugada syndrome 3;CN260585:Long qt syndrome 8 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Sep 30, 2021 | - - |
Long QT syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 19, 2024 | - - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 02, 2022 | 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