rs1553292962
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PP2PP3_Moderate
The NM_024529.5(CDC73):c.1438T>G(p.Tyr480Asp) 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. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Y480C) has been classified as Uncertain significance.
Frequency
Consequence
NM_024529.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CDC73 | NM_024529.5 | c.1438T>G | p.Tyr480Asp | missense_variant | 16/17 | ENST00000367435.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CDC73 | ENST00000367435.5 | c.1438T>G | p.Tyr480Asp | missense_variant | 16/17 | 1 | NM_024529.5 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome Cov.: 29
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Parathyroid carcinoma Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 02, 2023 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on CDC73 protein function. ClinVar contains an entry for this variant (Variation ID: 462748). This variant has not been reported in the literature in individuals affected with CDC73-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces tyrosine, which is neutral and polar, with aspartic acid, which is acidic and polar, at codon 480 of the CDC73 protein (p.Tyr480Asp). - |
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 14, 2023 | The p.Y480D variant (also known as c.1438T>G), located in coding exon 16 of the CDC73 gene, results from a T to G substitution at nucleotide position 1438. The tyrosine at codon 480 is replaced by aspartic acid, an amino acid with highly dissimilar properties. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at