chr1-201039833-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_000069.3(CACNA1S):c.5620T>C(p.Ter1874ArgextTer13) 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
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CACNA1S | NM_000069.3 | c.5620T>C | p.Ter1874ArgextTer13 | stop_lost | 44/44 | ENST00000362061.4 | |
LOC101929305 | XR_922410.3 | n.1378-2022A>G | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CACNA1S | ENST00000362061.4 | c.5620T>C | p.Ter1874ArgextTer13 | stop_lost | 44/44 | 1 | NM_000069.3 | P2 | |
ENST00000415359.1 | n.211-2022A>G | intron_variant, non_coding_transcript_variant | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 34
GnomAD3 genomes
?
Cov.:
34
GnomAD4 exome AF: 0.00000551 AC: 8AN: 1451530Hom.: 0 Cov.: 31 AF XY: 0.00000554 AC XY: 4AN XY: 722528
GnomAD4 exome
AF:
AC:
8
AN:
1451530
Hom.:
Cov.:
31
AF XY:
AC XY:
4
AN XY:
722528
Gnomad4 AFR exome
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GnomAD4 genome ? Cov.: 34
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
Uncertain significance, no assertion criteria provided | research | Gharavi Laboratory, Columbia University | Sep 16, 2018 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
Cadd
Benign
Dann
Benign
Eigen
Pathogenic
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
MutationTaster
Benign
N;N
Vest4
GERP RS
Splicing
Name
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at