3-39091638-A-G

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_020839.4(WDR48):ā€‹c.1682A>Gā€‹(p.Lys561Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000522 in 1,605,432 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: š‘“ 0.00055 ( 1 hom., cov: 32)
Exomes š‘“: 0.00052 ( 10 hom. )

Consequence

WDR48
NM_020839.4 missense

Scores

1
7
11

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 7.46
Variant links:
Genes affected
WDR48 (HGNC:30914): (WD repeat domain 48) The protein encoded by this gene has been shown to interact with ubiquitin specific peptidase 1 (USP1), activating the deubiquitinating activity of USP1 and allowing it to remove the ubiquitin moiety from monoubiquitinated FANCD2. FANCD2 is ubiquitinated in response to DNA damage. [provided by RefSeq, Sep 2016]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.010613382).
BP6
Variant 3-39091638-A-G is Benign according to our data. Variant chr3-39091638-A-G is described in ClinVar as [Benign]. Clinvar id is 3050664.Status of the report is no_assertion_criteria_provided, 0 stars.
BS2
High AC in GnomAd4 at 83 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
WDR48NM_020839.4 linkc.1682A>G p.Lys561Arg missense_variant Exon 17 of 19 ENST00000302313.10 NP_065890.1 Q8TAF3-1A0A024R2L1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
WDR48ENST00000302313.10 linkc.1682A>G p.Lys561Arg missense_variant Exon 17 of 19 1 NM_020839.4 ENSP00000307491.5 Q8TAF3-1

Frequencies

GnomAD3 genomes
AF:
0.000545
AC:
83
AN:
152156
Hom.:
1
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
Gnomad ASJ
AF:
0.0205
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000162
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00105
AC:
255
AN:
241856
Hom.:
7
AF XY:
0.000948
AC XY:
124
AN XY:
130764
show subpopulations
Gnomad AFR exome
AF:
0.0000636
Gnomad AMR exome
AF:
0.0000314
Gnomad ASJ exome
AF:
0.0218
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000297
Gnomad OTH exome
AF:
0.000851
GnomAD4 exome
AF:
0.000520
AC:
755
AN:
1453276
Hom.:
10
Cov.:
30
AF XY:
0.000505
AC XY:
365
AN XY:
722658
show subpopulations
Gnomad4 AFR exome
AF:
0.0000606
Gnomad4 AMR exome
AF:
0.0000235
Gnomad4 ASJ exome
AF:
0.0217
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000892
Gnomad4 OTH exome
AF:
0.00150
GnomAD4 genome
AF:
0.000545
AC:
83
AN:
152156
Hom.:
1
Cov.:
32
AF XY:
0.000552
AC XY:
41
AN XY:
74334
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000655
Gnomad4 ASJ
AF:
0.0205
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000162
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.00112
Hom.:
7
Bravo
AF:
0.000695
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.00128
AC:
11
ExAC
AF:
0.000923
AC:
112
EpiCase
AF:
0.000276
EpiControl
AF:
0.000482

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

WDR48-related disorder Benign:1
Benign, no assertion criteria providedclinical testingPreventionGenetics, part of Exact SciencesJul 26, 2019This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.14
BayesDel_addAF
Benign
-0.18
T
BayesDel_noAF
Benign
-0.19
CADD
Benign
22
DANN
Uncertain
1.0
DEOGEN2
Benign
0.15
T
Eigen
Uncertain
0.35
Eigen_PC
Uncertain
0.46
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.95
D
M_CAP
Benign
0.035
D
MetaRNN
Benign
0.011
T
MetaSVM
Uncertain
0.20
D
MutationAssessor
Benign
1.7
L
PrimateAI
Uncertain
0.68
T
PROVEAN
Benign
-2.2
N
REVEL
Uncertain
0.34
Sift
Benign
0.050
D
Sift4G
Benign
0.21
T
Polyphen
0.41
B
Vest4
0.57
MVP
0.28
MPC
0.68
ClinPred
0.071
T
GERP RS
4.6
Varity_R
0.50
gMVP
0.24

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.

Other links and lift over

dbSNP: rs139870313; hg19: chr3-39133129; COSMIC: COSV56531975; API