Variant 14-102140045-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_144574.4(WDR20):c.122A>G(p.Asn41Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000342 in 1,461,888 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

WDR20
NM_144574.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.73

Variant links:

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]

WDR20 links:

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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=0.24725845).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WDR20	NM_144574.4 linkuse as main transcript	c.122A>G	p.Asn41Ser	missense_variant	1/3	ENST00000342702.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WDR20	ENST00000342702.8 linkuse as main transcript	c.122A>G	p.Asn41Ser	missense_variant	1/3	1	NM_144574.4		Q8TBZ3-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000795

AC:

AN:

251436

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135922

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1461888

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

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

Apr 07, 2023

The c.122A>G (p.N41S) alteration is located in exon 1 (coding exon 1) of the WDR20 gene. This alteration results from a A to G substitution at nucleotide position 122, causing the asparagine (N) at amino acid position 41 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.55

CADD

Uncertain

DANN

Benign

0.97

DEOGEN2

Benign

0.21

.;.;.;T;.;T;.;.;.

Eigen

Benign

0.11

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Benign

0.57

LIST_S2

Uncertain

0.91

D;D;D;D;D;D;D;D;D

M_CAP

Benign

0.028

MetaRNN

Benign

0.25

T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.5

L;.;L;L;L;.;L;L;L

MutationTaster

Benign

1.0

D;D;D;D;D;D;D;D;D;D

PrimateAI

Uncertain

0.68

PROVEAN

Benign

-1.6

N;.;N;N;N;N;N;N;N

REVEL

Benign

0.11

Sift

Benign

0.38

T;.;T;T;T;T;T;T;T

Sift4G

Benign

0.42

T;T;T;T;T;T;T;T;T

Polyphen

0.035

B;.;.;B;.;.;.;.;.

Vest4

0.47

MutPred

0.22

Gain of catalytic residue at R37 (P = 0.0482);Gain of catalytic residue at R37 (P = 0.0482);Gain of catalytic residue at R37 (P = 0.0482);Gain of catalytic residue at R37 (P = 0.0482);Gain of catalytic residue at R37 (P = 0.0482);Gain of catalytic residue at R37 (P = 0.0482);Gain of catalytic residue at R37 (P = 0.0482);Gain of catalytic residue at R37 (P = 0.0482);Gain of catalytic residue at R37 (P = 0.0482);

MVP

0.26

MPC

0.38

ClinPred

0.53

GERP RS

5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.42

gMVP

0.72

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over