chr1-193147940-G-C
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP2
The NM_024529.5(CDC73):āc.803G>Cā(p.Arg268Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,660 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R268Q) 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 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CDC73 | NM_024529.5 | c.803G>C | p.Arg268Pro | missense_variant | 8/17 | ENST00000367435.5 | |
CDC73 | XM_006711537.5 | c.803G>C | p.Arg268Pro | missense_variant | 8/11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CDC73 | ENST00000367435.5 | c.803G>C | p.Arg268Pro | missense_variant | 8/17 | 1 | NM_024529.5 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome AF: 6.85e-7 AC: 1AN: 1460660Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0AN XY: 726770
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Parathyroid carcinoma Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 09, 2019 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with CDC73-related conditions. ClinVar contains an entry for this variant (Variation ID: 462768). This variant is not present in population databases (ExAC no frequency). This sequence change replaces arginine with proline at codon 268 of the CDC73 protein (p.Arg268Pro). The arginine residue is moderately conserved and there is a moderate physicochemical difference between arginine and proline. - |
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 30, 2022 | The p.R268P variant (also known as c.803G>C), located in coding exon 8 of the CDC73 gene, results from a G to C substitution at nucleotide position 803. The arginine at codon 268 is replaced by proline, an amino acid with dissimilar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. 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