rs200848930
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP6
The NM_000069.3(CACNA1S):c.4882C>T(p.Leu1628Phe) variant causes a missense change. The variant allele was found at a frequency of 0.0000781 in 1,614,126 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. L1628P) has been classified as Uncertain significance.
Frequency
Consequence
NM_000069.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CACNA1S | NM_000069.3 | c.4882C>T | p.Leu1628Phe | missense_variant | 40/44 | ENST00000362061.4 | |
CACNA1S | XM_005245478.4 | c.4825C>T | p.Leu1609Phe | missense_variant | 39/43 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CACNA1S | ENST00000362061.4 | c.4882C>T | p.Leu1628Phe | missense_variant | 40/44 | 1 | NM_000069.3 | P2 |
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152126Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000398 AC: 10AN: 251460Hom.: 0 AF XY: 0.0000515 AC XY: 7AN XY: 135910
GnomAD4 exome AF: 0.0000821 AC: 120AN: 1461882Hom.: 0 Cov.: 31 AF XY: 0.0000825 AC XY: 60AN XY: 727238
GnomAD4 genome AF: 0.0000394 AC: 6AN: 152244Hom.: 0 Cov.: 31 AF XY: 0.0000672 AC XY: 5AN XY: 74426
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jun 01, 2021 | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 26582918, 27535533) - |
Uncertain significance, criteria provided, single submitter | clinical testing | Athena Diagnostics | May 11, 2018 | - - |
Hypokalemic periodic paralysis Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Malignant hyperthermia of anesthesia Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Malignant hyperthermia, susceptibility to, 5;C3714580:Hypokalemic periodic paralysis, type 1 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 17, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at