15-84643544-T-A
Variant names:
Variant summary
Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM1PM2
The NM_032856.5(WDR73):c.1063A>T(p.Arg355Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. R355G) has been classified as Uncertain significance.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
WDR73
NM_032856.5 missense
NM_032856.5 missense
Scores
1
7
11
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 2.14
Publications
0 publications found
Genes affected
WDR73 (HGNC:25928): (WD repeat domain 73) The protein encoded by this gene is thought to contain multiple WD40 repeats. WD40 repeats are motifs that contain 40-60 amino acids, and usually end with Trp-Asp (WD). This protein is found in the cytoplasm during interphase, but accumulates at the spindle poles and astral microtubules during mitosis. Reduced expression of this gene results in abnormalities in the size and morphology of the nucleus. Mutations in this gene have been associated with Galloway-Mowat syndrome PMID: 25466283), which is a rare autosomal recessive disorder that affects both the central nervous system and kidneys. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2015]
WDR73 Gene-Disease associations (from GenCC):
- Galloway-Mowat syndrome 1Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
- CAMOS syndromeInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
- Galloway-Mowat syndromeInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
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ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 4 ACMG points.
PM1
In a hotspot region, there are 2 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 0 benign, 3 uncertain in NM_032856.5
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1455268Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 723154
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
1455268
Hom.:
Cov.:
33
AF XY:
AC XY:
0
AN XY:
723154
African (AFR)
AF:
AC:
0
AN:
33434
American (AMR)
AF:
AC:
0
AN:
43656
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
25922
East Asian (EAS)
AF:
AC:
0
AN:
39550
South Asian (SAS)
AF:
AC:
0
AN:
84780
European-Finnish (FIN)
AF:
AC:
0
AN:
53074
Middle Eastern (MID)
AF:
AC:
0
AN:
5758
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1108930
Other (OTH)
AF:
AC:
0
AN:
60164
GnomAD4 genome
GnomAD4 genome
Cov.:
32
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D
M_CAP
Benign
D
MetaRNN
Uncertain
D
MetaSVM
Benign
T
MutationAssessor
Benign
M
PhyloP100
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Pathogenic
D
Polyphen
D
Vest4
MutPred
Loss of methylation at R355 (P = 0.0348);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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