14-102209153-G-T
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_144574.4(WDR20):c.983G>T(p.Ser328Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000031 in 1,613,806 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000033 ( 0 hom. )
Consequence
WDR20
NM_144574.4 missense
NM_144574.4 missense
Scores
5
10
4
Clinical Significance
Conservation
PhyloP100: 9.59
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
WDR20 | NM_144574.4 | c.983G>T | p.Ser328Ile | 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.983G>T | p.Ser328Ile | missense_variant | 3/3 | 1 | NM_144574.4 | ENSP00000341037 |
Frequencies
GnomAD3 genomes AF: 0.0000132 AC: 2AN: 151912Hom.: 0 Cov.: 32
GnomAD3 genomes
AF:
AC:
2
AN:
151912
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.0000278 AC: 7AN: 251446Hom.: 0 AF XY: 0.0000294 AC XY: 4AN XY: 135902
GnomAD3 exomes
AF:
AC:
7
AN:
251446
Hom.:
AF XY:
AC XY:
4
AN XY:
135902
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000328 AC: 48AN: 1461894Hom.: 0 Cov.: 32 AF XY: 0.0000385 AC XY: 28AN XY: 727248
GnomAD4 exome
AF:
AC:
48
AN:
1461894
Hom.:
Cov.:
32
AF XY:
AC XY:
28
AN XY:
727248
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.0000132 AC: 2AN: 151912Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74220
GnomAD4 genome
AF:
AC:
2
AN:
151912
Hom.:
Cov.:
32
AF XY:
AC XY:
1
AN XY:
74220
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Bravo
AF:
TwinsUK
AF:
AC:
2
ALSPAC
AF:
AC:
0
ExAC
AF:
AC:
5
EpiCase
AF:
EpiControl
AF:
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 | Oct 04, 2022 | The c.1076G>T (p.S359I) alteration is located in exon 4 (coding exon 4) of the WDR20 gene. This alteration results from a G to T substitution at nucleotide position 1076, causing the serine (S) at amino acid position 359 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Uncertain
.;.;D;.;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D;D;D;D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D;D;D;D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.;M;.;.;.
MutationTaster
Benign
D;D;D;D;D;D;D;D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
D;D;D;D;D;D
REVEL
Uncertain
Sift
Benign
T;D;T;D;T;D
Sift4G
Uncertain
D;D;D;D;D;D
Polyphen
P;.;P;.;.;.
Vest4
MutPred
Loss of glycosylation at S328 (P = 0.0112);.;Loss of glycosylation at S328 (P = 0.0112);.;.;.;
MVP
MPC
0.59
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at