rs183440052
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Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7
The NM_000069.3(CACNA1S):c.4995C>T(p.Asn1665=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000409 in 1,614,210 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 Likely benign (★★).
Frequency
Genomes: 𝑓 0.00012 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000033 ( 0 hom. )
Consequence
CACNA1S
NM_000069.3 synonymous
NM_000069.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.122
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 Benign. Variant got -11 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.7).
BP6
?
Variant 1-201043334-G-A is Benign according to our data. Variant chr1-201043334-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 473999.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-0.122 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CACNA1S | NM_000069.3 | c.4995C>T | p.Asn1665= | synonymous_variant | 40/44 | ENST00000362061.4 | |
CACNA1S | XM_005245478.4 | c.4938C>T | p.Asn1646= | synonymous_variant | 39/43 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CACNA1S | ENST00000362061.4 | c.4995C>T | p.Asn1665= | synonymous_variant | 40/44 | 1 | NM_000069.3 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.000118 AC: 18AN: 152208Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000517 AC: 13AN: 251404Hom.: 0 AF XY: 0.0000294 AC XY: 4AN XY: 135890
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GnomAD4 exome AF: 0.0000328 AC: 48AN: 1461884Hom.: 0 Cov.: 31 AF XY: 0.0000385 AC XY: 28AN XY: 727244
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GnomAD4 genome ? AF: 0.000118 AC: 18AN: 152326Hom.: 0 Cov.: 32 AF XY: 0.000134 AC XY: 10AN XY: 74484
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Malignant hyperthermia, susceptibility to, 5;C3714580:Hypokalemic periodic paralysis, type 1 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 19, 2024 | - - |
Malignant hyperthermia, susceptibility to, 5 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | All of Us Research Program, National Institutes of Health | Dec 01, 2023 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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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