chr1-43360010-A-C
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM1PM2BP4
The NM_001255.3(CDC20):c.469A>C(p.Thr157Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000124 in 1,613,624 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000013 ( 0 hom. )
Consequence
CDC20
NM_001255.3 missense
NM_001255.3 missense
Scores
1
6
11
Clinical Significance
Conservation
PhyloP100: 9.32
Genes affected
CDC20 (HGNC:1723): (cell division cycle 20) CDC20 appears to act as a regulatory protein interacting with several other proteins at multiple points in the cell cycle. It is required for two microtubule-dependent processes, nuclear movement prior to anaphase and chromosome separation. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM1
?
In a mutagenesis_site Loss of BUB1-mediated phosphorylation and inhibition and partially defective spindle-assembly checkpoint; when associated with A-42; A-72; A-92; A-153 and A-161. (size 0) in uniprot entity CDC20_HUMAN
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.3141326).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CDC20 | NM_001255.3 | c.469A>C | p.Thr157Pro | missense_variant | 5/11 | ENST00000310955.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CDC20 | ENST00000310955.11 | c.469A>C | p.Thr157Pro | missense_variant | 5/11 | 1 | NM_001255.3 | P1 | |
CDC20 | ENST00000372462.1 | c.469A>C | p.Thr157Pro | missense_variant | 4/10 | 1 | P1 | ||
CDC20 | ENST00000478882.1 | n.244A>C | non_coding_transcript_exon_variant | 1/4 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 151872Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251442Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135904
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GnomAD4 exome AF: 0.0000130 AC: 19AN: 1461752Hom.: 0 Cov.: 35 AF XY: 0.00000688 AC XY: 5AN XY: 727170
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 10, 2021 | The c.469A>C (p.T157P) alteration is located in exon 5 (coding exon 4) of the CDC20 gene. This alteration results from a A to C substitution at nucleotide position 469, causing the threonine (T) at amino acid position 157 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
DEOGEN2
Benign
T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;L
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D
REVEL
Benign
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
B;B
Vest4
MutPred
Loss of sheet (P = 0.0025);Loss of sheet (P = 0.0025);
MVP
MPC
0.52
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at