rs121434264
Variant summary
Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PM2PP2PP3_StrongPP5_Moderate
The NM_024529.5(CDC73):c.191T>C(p.Leu64Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 13/21 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. L64L) has been classified as Likely benign.
Frequency
Consequence
NM_024529.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CDC73 | NM_024529.5 | c.191T>C | p.Leu64Pro | missense_variant | 2/17 | ENST00000367435.5 | |
CDC73 | XM_006711537.5 | c.191T>C | p.Leu64Pro | missense_variant | 2/11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CDC73 | ENST00000367435.5 | c.191T>C | p.Leu64Pro | missense_variant | 2/17 | 1 | NM_024529.5 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome Cov.: 28
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Hyperparathyroidism 1 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Dec 01, 2002 | - - |
Parathyroid carcinoma Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Invitae | Apr 04, 2021 | In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Experimental studies have shown that this variant affects CDC73 protein function (PMID: 15580289, 15632063). This variant has been observed in individual(s) with clinical features of CDC73-related conditions (PMID: 12434154, 14985403, 19017757). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 3272). This variant is not present in population databases (ExAC no frequency). This sequence change replaces leucine with proline at codon 64 of the CDC73 protein (p.Leu64Pro). The leucine residue is highly conserved and there is a moderate physicochemical difference between leucine and proline. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at