chr1-117933344-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_006784.3(WDR3):​c.25C>T​(p.Arg9Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000102 in 1,614,050 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00011 ( 2 hom. )

Consequence

WDR3
NM_006784.3 missense

Scores

6
9
4

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.74
Variant links:
Genes affected
WDR3 (HGNC:12755): (WD repeat domain 3) This gene encodes a nuclear protein containing 10 WD repeats. WD repeats are approximately 30- to 40-amino acid domains containing several conserved residues, which usually include a trp-asp at the C-terminal end. Proteins belonging to the WD repeat family are involved in a variety of cellular processes, including cell cycle progression, signal transduction, apoptosis, and gene regulation. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2
High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
WDR3NM_006784.3 linkuse as main transcriptc.25C>T p.Arg9Cys missense_variant 2/27 ENST00000349139.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
WDR3ENST00000349139.6 linkuse as main transcriptc.25C>T p.Arg9Cys missense_variant 2/271 NM_006784.3 P1
WDR3ENST00000369441.7 linkuse as main transcriptc.25C>T p.Arg9Cys missense_variant 2/101
WDR3ENST00000471680.1 linkuse as main transcriptn.207C>T non_coding_transcript_exon_variant 2/55
WDR3ENST00000487202.5 linkuse as main transcriptn.116C>T non_coding_transcript_exon_variant 2/63

Frequencies

GnomAD3 genomes
AF:
0.0000657
AC:
10
AN:
152188
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000828
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000882
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000135
AC:
34
AN:
251458
Hom.:
0
AF XY:
0.000213
AC XY:
29
AN XY:
135900
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000882
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000615
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000105
AC:
154
AN:
1461862
Hom.:
2
Cov.:
30
AF XY:
0.000151
AC XY:
110
AN XY:
727238
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000858
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000683
Gnomad4 OTH exome
AF:
0.0000662
GnomAD4 genome
AF:
0.0000657
AC:
10
AN:
152188
Hom.:
0
Cov.:
32
AF XY:
0.0000538
AC XY:
4
AN XY:
74346
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000828
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000882
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000675
Hom.:
0
Bravo
AF:
0.0000453
TwinsUK
AF:
0.000270
AC:
1
ALSPAC
AF:
0.00
AC:
0
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.000123
AC:
15
Asia WGS
AF:
0.000577
AC:
2
AN:
3478
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

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 submitterclinical testingAmbry GeneticsAug 02, 2021The c.25C>T (p.R9C) alteration is located in exon 2 (coding exon 1) of the WDR3 gene. This alteration results from a C to T substitution at nucleotide position 25, causing the arginine (R) at amino acid position 9 to be replaced by a cysteine (C). 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
Pathogenic
0.58
BayesDel_addAF
Benign
0.011
T
BayesDel_noAF
Pathogenic
0.18
CADD
Pathogenic
28
DANN
Uncertain
0.99
DEOGEN2
Benign
0.20
T;T
Eigen
Uncertain
0.36
Eigen_PC
Uncertain
0.42
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.94
D;D
M_CAP
Uncertain
0.15
D
MetaRNN
Uncertain
0.44
T;T
MetaSVM
Benign
-0.57
T
MutationAssessor
Uncertain
2.7
.;M
MutationTaster
Benign
1.0
D;D
PrimateAI
Pathogenic
0.83
D
PROVEAN
Pathogenic
-7.5
D;D
REVEL
Uncertain
0.44
Sift
Uncertain
0.022
.;D
Sift4G
Pathogenic
0.0
D;D
Polyphen
0.40
.;B
Vest4
0.80
MVP
0.75
MPC
0.25
ClinPred
0.48
T
GERP RS
5.1
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.52
gMVP
0.79

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: rs376572237; hg19: chr1-118475967; COSMIC: COSV62522519; COSMIC: COSV62522519; API