rs876657376
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Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_000782.5(CYP24A1):c.1426_1427del(p.Cys477LeufsTer14) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 33)
Consequence
CYP24A1
NM_000782.5 frameshift
NM_000782.5 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 8.55
Genes affected
CYP24A1 (HGNC:2602): (cytochrome P450 family 24 subfamily A member 1) This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This mitochondrial protein initiates the degradation of 1,25-dihydroxyvitamin D3, the physiologically active form of vitamin D3, by hydroxylation of the side chain. In regulating the level of vitamin D3, this enzyme plays a role in calcium homeostasis and the vitamin D endocrine system. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 11 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 20-54157394-AAG-A is Pathogenic according to our data. Variant chr20-54157394-AAG-A is described in ClinVar as [Pathogenic]. Clinvar id is 29675.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CYP24A1 | NM_000782.5 | c.1426_1427del | p.Cys477LeufsTer14 | frameshift_variant | 10/12 | ENST00000216862.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CYP24A1 | ENST00000216862.8 | c.1426_1427del | p.Cys477LeufsTer14 | frameshift_variant | 10/12 | 1 | NM_000782.5 | P1 | |
CYP24A1 | ENST00000395954.3 | c.1000_1001del | p.Cys335LeufsTer14 | frameshift_variant | 8/10 | 1 | |||
CYP24A1 | ENST00000395955.7 | c.1237-107_1237-106del | intron_variant | 1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251442Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135890
GnomAD3 exomes
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1
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251442
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1
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135890
Gnomad AFR exome
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We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
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33
Bravo
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Hypercalcemia, infantile, 1 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Aug 04, 2011 | - - |
Computational scores
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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