rs143202536
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM2PP3_ModerateBP6
The ENST00000362061.4(CACNA1S):c.1382C>T(p.Thr461Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000477 in 1,614,052 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 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. T461N) has been classified as Uncertain significance.
Frequency
Consequence
ENST00000362061.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CACNA1S | NM_000069.3 | c.1382C>T | p.Thr461Ile | missense_variant | 10/44 | ENST00000362061.4 | NP_000060.2 | |
CACNA1S | XM_005245478.4 | c.1382C>T | p.Thr461Ile | missense_variant | 10/43 | XP_005245535.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CACNA1S | ENST00000362061.4 | c.1382C>T | p.Thr461Ile | missense_variant | 10/44 | 1 | NM_000069.3 | ENSP00000355192 | P2 |
Frequencies
GnomAD3 genomes AF: 0.000282 AC: 43AN: 152220Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000597 AC: 15AN: 251276Hom.: 0 AF XY: 0.0000663 AC XY: 9AN XY: 135836
GnomAD4 exome AF: 0.0000233 AC: 34AN: 1461832Hom.: 0 Cov.: 31 AF XY: 0.0000248 AC XY: 18AN XY: 727214
GnomAD4 genome AF: 0.000282 AC: 43AN: 152220Hom.: 0 Cov.: 33 AF XY: 0.000323 AC XY: 24AN XY: 74370
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 18, 2021 | The c.1382C>T (p.T461I) alteration is located in exon 10 (coding exon 10) of the CACNA1S gene. This alteration results from a C to T substitution at nucleotide position 1382, causing the threonine (T) at amino acid position 461 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Malignant hyperthermia, susceptibility to, 5;C3714580:Hypokalemic periodic paralysis, type 1 Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 18, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at