1-201039833-A-G
Variant names:
Variant summary
Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM4
The NM_000069.3(CACNA1S):c.5620T>C(p.Ter1874Argext*?) variant causes a stop lost change. The variant allele was found at a frequency of 0.00000551 in 1,451,530 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (no stars).
Frequency
Genomes: not found (cov: 34)
Exomes 𝑓: 0.0000055 ( 0 hom. )
Consequence
CACNA1S
NM_000069.3 stop_lost
NM_000069.3 stop_lost
Scores
1
4
2
Clinical Significance
Conservation
PhyloP100: 3.64
Publications
0 publications found
Genes affected
CACNA1S (HGNC:1397): (calcium voltage-gated channel subunit alpha1 S) This gene encodes one of the five subunits of the slowly inactivating L-type voltage-dependent calcium channel in skeletal muscle cells. Mutations in this gene have been associated with hypokalemic periodic paralysis, thyrotoxic periodic paralysis and malignant hyperthermia susceptibility. [provided by RefSeq, Jul 2008]
CACNA1S Gene-Disease associations (from GenCC):
- 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
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 2 ACMG points.
PM4
Stoplost variant in NM_000069.3 Downstream stopcodon found after 1902 codons.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
34
GnomAD4 exome AF: 0.00000551 AC: 8AN: 1451530Hom.: 0 Cov.: 31 AF XY: 0.00000554 AC XY: 4AN XY: 722528 show subpopulations
GnomAD4 exome
AF:
AC:
8
AN:
1451530
Hom.:
Cov.:
31
AF XY:
AC XY:
4
AN XY:
722528
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33478
American (AMR)
AF:
AC:
0
AN:
44722
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26136
East Asian (EAS)
AF:
AC:
0
AN:
39698
South Asian (SAS)
AF:
AC:
0
AN:
86258
European-Finnish (FIN)
AF:
AC:
0
AN:
43178
Middle Eastern (MID)
AF:
AC:
0
AN:
5766
European-Non Finnish (NFE)
AF:
AC:
7
AN:
1111958
Other (OTH)
AF:
AC:
1
AN:
60336
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.488
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
GnomAD4 genome
Cov.:
34
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
not provided Uncertain:1
Sep 16, 2018
Gharavi Laboratory, Columbia University
Significance:Uncertain significance
Review Status:no assertion criteria provided
Collection Method:research
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
DANN
Benign
Eigen
Pathogenic
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
PhyloP100
Vest4
GERP RS
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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