NM_000069.3:c.5238G>A
Variant summary
Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6BP7
The NM_000069.3(CACNA1S):c.5238G>A(p.Val1746Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000372 in 1,613,304 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_000069.3 synonymous
Scores
Clinical Significance
Conservation
Publications
- congenital myopathy 18Inheritance: AD, AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
- hypokalemic periodic paralysis, type 1Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Ambry Genetics
- malignant hyperthermia, susceptibility to, 5Inheritance: AD Classification: STRONG, MODERATE Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Ambry Genetics
- congenital myopathyInheritance: SD, AR, AD Classification: STRONG Submitted by: Illumina, Genomics England PanelApp
- hypokalemic periodic paralysisInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
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ACMG classification
Our verdict: Likely_benign. The variant received -6 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152224Hom.: 0 Cov.: 33 show subpopulations
GnomAD2 exomes AF: 0.00000802 AC: 2AN: 249476 AF XY: 0.00000740 show subpopulations
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461080Hom.: 0 Cov.: 33 AF XY: 0.00000275 AC XY: 2AN XY: 726806 show subpopulations
Age Distribution
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152224Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74358 show subpopulations
Age Distribution
ClinVar
Submissions by phenotype
Malignant hyperthermia, susceptibility to, 5 Uncertain:1
This variant is located in the CACNA1S protein. To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with CACNA1S-related disorders in the literature. This variant has been identified in 3/280856 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. -
Malignant hyperthermia, susceptibility to, 5;C3714580:Hypokalemic periodic paralysis, type 1 Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at