rs121434265
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_024529.5(CDC73):c.162C>G(p.Tyr54Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. Y54Y) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_024529.5 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CDC73 | NM_024529.5 | c.162C>G | p.Tyr54Ter | stop_gained | 2/17 | ENST00000367435.5 | |
CDC73 | XM_006711537.5 | c.162C>G | p.Tyr54Ter | stop_gained | 2/11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CDC73 | ENST00000367435.5 | c.162C>G | p.Tyr54Ter | stop_gained | 2/17 | 1 | NM_024529.5 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome Cov.: 28
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Parathyroid carcinoma Pathogenic:2
Pathogenic, no assertion criteria provided | literature only | OMIM | Oct 30, 2003 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jan 18, 2021 | For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals with CDC73-related conditions. ClinVar contains an entry for this variant (Variation ID: 3274). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Tyr54*) in the CDC73 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CDC73 are known to be pathogenic (PMID: 12434154). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at