NM_001029896.2:c.397C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001029896.2(WDR45):​c.397C>G​(p.Arg133Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000911 in 1,098,130 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R133Q) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 23)
Exomes 𝑓: 9.1e-7 ( 0 hom. 0 hem. )

Consequence

WDR45
NM_001029896.2 missense

Scores

3
14

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.25

Publications

0 publications found
Variant links:
Genes affected
WDR45 (HGNC:28912): (WD repeat domain 45) This gene encodes a member of the WD repeat protein family. WD repeats are minimally conserved regions of approximately 40 amino acids typically bracketed by gly-his and trp-asp (GH-WD), which may facilitate formation of heterotrimeric or multiprotein complexes. Members of this family are involved in a variety of cellular processes, including cell cycle progression, signal transduction, apoptosis, and gene regulation. This gene has a pseudogene at chromosome 4q31.3. Multiple alternatively spliced transcript variants encoding distinct isoforms have been found for this gene, but the biological validity and full-length nature of some variants have not been determined. [provided by RefSeq, Jul 2008]
WDR45 Gene-Disease associations (from GenCC):
  • neurodegeneration with brain iron accumulation 5
    Inheritance: XL Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Illumina, Labcorp Genetics (formerly Invitae), Ambry Genetics, Genomics England PanelApp, G2P
  • X-linked complex neurodevelopmental disorder
    Inheritance: XL Classification: DEFINITIVE Submitted by: ClinGen
  • infantile spasms
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.21925968).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
WDR45NM_001029896.2 linkc.397C>G p.Arg133Gly missense_variant Exon 6 of 11 ENST00000376372.9 NP_001025067.1 Q9Y484-1A0A024QYX1
WDR45NM_007075.4 linkc.400C>G p.Arg134Gly missense_variant Exon 7 of 12 NP_009006.2 Q9Y484-3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
WDR45ENST00000376372.9 linkc.397C>G p.Arg133Gly missense_variant Exon 6 of 11 1 NM_001029896.2 ENSP00000365551.3 Q9Y484-1
ENSG00000288053ENST00000376358.4 linkc.131-524C>G intron_variant Intron 3 of 7 2 ENSP00000365536.3 A6NM71

Frequencies

GnomAD3 genomes
Cov.:
23
GnomAD4 exome
AF:
9.11e-7
AC:
1
AN:
1098130
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
363516
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
26399
American (AMR)
AF:
0.00
AC:
0
AN:
35199
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
19385
East Asian (EAS)
AF:
0.00
AC:
0
AN:
30206
South Asian (SAS)
AF:
0.00
AC:
0
AN:
54142
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
40531
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
4067
European-Non Finnish (NFE)
AF:
0.00000119
AC:
1
AN:
842116
Other (OTH)
AF:
0.00
AC:
0
AN:
46085
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
Cov.:
23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.21
BayesDel_addAF
Benign
-0.032
T
BayesDel_noAF
Benign
-0.28
CADD
Benign
20
DANN
Uncertain
0.98
DEOGEN2
Benign
0.23
T;T;.;.;.;.;T;.;T;T;T;.;T;T;.;.;T;T
FATHMM_MKL
Benign
0.23
N
LIST_S2
Uncertain
0.94
.;D;D;D;.;D;D;D;D;D;D;D;D;D;D;D;D;D
M_CAP
Benign
0.056
D
MetaRNN
Benign
0.22
T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
-0.64
T
MutationAssessor
Benign
1.7
L;L;.;L;.;.;.;.;.;.;.;.;.;.;.;.;.;.
PhyloP100
2.2
PrimateAI
Benign
0.47
T
PROVEAN
Uncertain
-2.9
D;.;.;D;D;D;D;D;.;.;D;.;D;.;.;D;D;.
REVEL
Benign
0.26
Sift
Benign
0.096
T;.;.;T;T;T;D;T;.;.;T;.;D;.;.;T;D;.
Sift4G
Benign
0.19
T;T;T;T;T;T;T;T;T;.;.;.;.;.;T;.;.;.
Polyphen
0.0010
B;B;.;B;B;B;B;B;.;.;.;.;.;.;.;.;.;.
Vest4
0.39
MutPred
0.41
Gain of ubiquitination at K134 (P = 0.0516);Gain of ubiquitination at K134 (P = 0.0516);Gain of ubiquitination at K134 (P = 0.0516);Gain of ubiquitination at K134 (P = 0.0516);.;.;Gain of ubiquitination at K134 (P = 0.0516);.;.;.;.;Gain of ubiquitination at K134 (P = 0.0516);.;.;Gain of ubiquitination at K134 (P = 0.0516);.;Gain of ubiquitination at K134 (P = 0.0516);.;
MVP
0.38
MPC
0.85
ClinPred
0.18
T
GERP RS
2.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.22
gMVP
0.51
Mutation Taster
=56/44
polymorphism

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

Other links and lift over

dbSNP: rs797046101; hg19: chrX-48934128; API