rs777947329
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_000782.5(CYP24A1):c.1039C>T(p.Gln347Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000304 in 1,613,828 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 Likely pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_000782.5 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CYP24A1 | NM_000782.5 | c.1039C>T | p.Gln347Ter | stop_gained | 8/12 | ENST00000216862.8 | NP_000773.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CYP24A1 | ENST00000216862.8 | c.1039C>T | p.Gln347Ter | stop_gained | 8/12 | 1 | NM_000782.5 | ENSP00000216862 | P1 | |
CYP24A1 | ENST00000395955.7 | c.1039C>T | p.Gln347Ter | stop_gained | 8/11 | 1 | ENSP00000379285 | |||
CYP24A1 | ENST00000395954.3 | c.613C>T | p.Gln205Ter | stop_gained | 6/10 | 1 | ENSP00000379284 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152154Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251442Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135898
GnomAD4 exome AF: 0.0000328 AC: 48AN: 1461674Hom.: 0 Cov.: 32 AF XY: 0.0000261 AC XY: 19AN XY: 727136
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152154Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74324
ClinVar
Submissions by phenotype
Hypercalcemia, infantile, 1 Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Dec 18, 2014 | The p.Gln347X variant in CYP24A1 has not been previously reported in individuals with disease. It has been identified in 1/67868 Eurpoean chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org). This nonsense variant leads to a premature termination codon at position 347 which is predicted to lead to a truncated or absent protein. Loss-of-function variants in the CYP24A1 gene have been shown to cause autosomal recessive infantile hypercalcemia. In summary, although additional studies are required to fully establish its clinical significance, the p.Gln347X variant in CYP24A1 is likely pathogenic. - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Molecular Diagnostics Lab, Nemours Children's Health, Delaware | Mar 13, 2015 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at