1-117934657-G-T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_006784.3(WDR3):​c.356G>T​(p.Gly119Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000558 in 1,613,530 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

WDR3
NM_006784.3 missense

Scores

10
6
3

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.25
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_pathogenic. Variant got 6 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.964

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
WDR3NM_006784.3 linkuse as main transcriptc.356G>T p.Gly119Val missense_variant 3/27 ENST00000349139.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
WDR3ENST00000349139.6 linkuse as main transcriptc.356G>T p.Gly119Val missense_variant 3/271 NM_006784.3 P1
WDR3ENST00000369441.7 linkuse as main transcriptc.*243G>T 3_prime_UTR_variant 4/101
WDR3ENST00000471680.1 linkuse as main transcriptn.538G>T non_coding_transcript_exon_variant 3/55
WDR3ENST00000487202.5 linkuse as main transcriptn.457G>T non_coding_transcript_exon_variant 4/63

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152238
Hom.:
0
Cov.:
33
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:
0.000192
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000398
AC:
10
AN:
251322
Hom.:
0
AF XY:
0.0000442
AC XY:
6
AN XY:
135854
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000544
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000547
AC:
8
AN:
1461292
Hom.:
0
Cov.:
30
AF XY:
0.00000550
AC XY:
4
AN XY:
726970
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000202
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152238
Hom.:
0
Cov.:
33
AF XY:
0.0000134
AC XY:
1
AN XY:
74378
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000192
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000756
ExAC
AF:
0.00000824
AC:
1

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 GeneticsJun 28, 2023The c.356G>T (p.G119V) alteration is located in exon 3 (coding exon 2) of the WDR3 gene. This alteration results from a G to T substitution at nucleotide position 356, causing the glycine (G) at amino acid position 119 to be replaced by a valine (V). 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
0.94
BayesDel_addAF
Uncertain
0.15
D
BayesDel_noAF
Pathogenic
0.34
CADD
Pathogenic
30
DANN
Uncertain
1.0
DEOGEN2
Benign
0.39
T
Eigen
Pathogenic
1.1
Eigen_PC
Pathogenic
1.1
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.93
D
M_CAP
Benign
0.068
D
MetaRNN
Pathogenic
0.96
D
MetaSVM
Uncertain
0.55
D
MutationAssessor
Pathogenic
3.7
H
MutationTaster
Benign
1.0
D;D
PrimateAI
Uncertain
0.59
T
PROVEAN
Pathogenic
-7.7
D
REVEL
Pathogenic
0.79
Sift
Uncertain
0.0010
D
Sift4G
Pathogenic
0.0010
D
Polyphen
1.0
D
Vest4
0.90
MutPred
0.87
Loss of disorder (P = 0.0213);
MVP
0.94
MPC
0.61
ClinPred
0.92
D
GERP RS
5.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.8
Varity_R
0.94
gMVP
0.71

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs767989957; hg19: chr1-118477280; API