14-102209401-G-C
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_144574.4(WDR20):āc.1231G>Cā(p.Ala411Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000044 in 1,614,050 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.000026 ( 0 hom., cov: 32)
Exomes š: 0.000046 ( 1 hom. )
Consequence
WDR20
NM_144574.4 missense
NM_144574.4 missense
Scores
4
15
Clinical Significance
Conservation
PhyloP100: 4.50
Genes affected
WDR20 (HGNC:19667): (WD repeat domain 20) This gene encodes a WD repeat-containing protein that functions to preserve and regulate the activity of the USP12-UAF1 deubiquitinating enzyme complex. Multiple alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jun 2011]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.07721713).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
WDR20 | NM_144574.4 | c.1231G>C | p.Ala411Pro | missense_variant | 3/3 | ENST00000342702.8 | NP_653175.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
WDR20 | ENST00000342702.8 | c.1231G>C | p.Ala411Pro | missense_variant | 3/3 | 1 | NM_144574.4 | ENSP00000341037 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152180Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000235 AC: 59AN: 251128Hom.: 1 AF XY: 0.000177 AC XY: 24AN XY: 135748
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GnomAD4 exome AF: 0.0000458 AC: 67AN: 1461870Hom.: 1 Cov.: 32 AF XY: 0.0000413 AC XY: 30AN XY: 727228
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GnomAD4 genome AF: 0.0000263 AC: 4AN: 152180Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74330
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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 | Dec 18, 2023 | The c.1324G>C (p.A442P) alteration is located in exon 4 (coding exon 4) of the WDR20 gene. This alteration results from a G to C substitution at nucleotide position 1324, causing the alanine (A) at amino acid position 442 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
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
.;.;T;.;.;.
Eigen
Benign
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T;T;T;T;T
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;.;L;.;.;.
MutationTaster
Benign
D;D;D;D;D;D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;.;N;N;N;N
REVEL
Benign
Sift
Benign
T;.;T;D;D;D
Sift4G
Benign
T;T;T;T;T;T
Polyphen
B;.;B;.;.;.
Vest4
MutPred
Gain of catalytic residue at P409 (P = 0.001);.;Gain of catalytic residue at P409 (P = 0.001);.;.;.;
MVP
MPC
0.63
ClinPred
T
GERP RS
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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