chr1-117942524-A-G

Variant summary

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

The NM_006784.3(WDR3):ā€‹c.1077A>Gā€‹(p.Ile359Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,528 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 6.8e-7 ( 0 hom. )

Consequence

WDR3
NM_006784.3 missense

Scores

7
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.779
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 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=0.24894619).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
WDR3NM_006784.3 linkuse as main transcriptc.1077A>G p.Ile359Met missense_variant 10/27 ENST00000349139.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
WDR3ENST00000349139.6 linkuse as main transcriptc.1077A>G p.Ile359Met missense_variant 10/271 NM_006784.3 P1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461528
Hom.:
0
Cov.:
30
AF XY:
0.00000138
AC XY:
1
AN XY:
727064
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:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378

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 GeneticsOct 13, 2023The c.1077A>G (p.I359M) alteration is located in exon 10 (coding exon 9) of the WDR3 gene. This alteration results from a A to G substitution at nucleotide position 1077, causing the isoleucine (I) at amino acid position 359 to be replaced by a methionine (M). 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
0.14
BayesDel_addAF
Benign
-0.080
T
BayesDel_noAF
Benign
-0.35
CADD
Benign
20
DANN
Uncertain
0.99
DEOGEN2
Benign
0.16
T
Eigen
Benign
-0.18
Eigen_PC
Benign
-0.21
FATHMM_MKL
Uncertain
0.85
D
LIST_S2
Uncertain
0.87
D
M_CAP
Benign
0.023
T
MetaRNN
Benign
0.25
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.7
M
MutationTaster
Benign
1.0
D
PrimateAI
Uncertain
0.49
T
PROVEAN
Benign
-2.3
N
REVEL
Benign
0.18
Sift
Uncertain
0.0030
D
Sift4G
Uncertain
0.0050
D
Polyphen
0.93
P
Vest4
0.34
MutPred
0.60
Gain of ubiquitination at K364 (P = 0.0338);
MVP
0.52
MPC
0.37
ClinPred
0.97
D
GERP RS
1.3
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.29
gMVP
0.39

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: rs1055806540; hg19: chr1-118485147; API