5-111092610-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_139281.3(WDR36):c.154A>G(p.Thr52Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,460,906 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T52I) has been classified as Uncertain significance.
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000027 ( 0 hom. )
Consequence
WDR36
NM_139281.3 missense
NM_139281.3 missense
Scores
3
7
7
Clinical Significance
Conservation
PhyloP100: 6.47
Genes affected
WDR36 (HGNC:30696): (WD repeat domain 36) 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. Mutations in this gene have been associated with adult-onset primary open-angle glaucoma (POAG). [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
WDR36 | NM_139281.3 | c.154A>G | p.Thr52Ala | missense_variant | 1/23 | ENST00000513710.4 | |
WDR36 | XM_047416729.1 | c.154A>G | p.Thr52Ala | missense_variant | 1/21 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
WDR36 | ENST00000513710.4 | c.154A>G | p.Thr52Ala | missense_variant | 1/23 | 1 | NM_139281.3 | P1 | |
WDR36 | ENST00000505303.5 | n.290A>G | non_coding_transcript_exon_variant | 1/15 | 5 | ||||
WDR36 | ENST00000515784.1 | n.264A>G | non_coding_transcript_exon_variant | 1/2 | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD3 exomes AF: 0.0000163 AC: 4AN: 246138Hom.: 0 AF XY: 0.0000150 AC XY: 2AN XY: 133346
GnomAD3 exomes
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GnomAD4 exome AF: 0.00000274 AC: 4AN: 1460906Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 726708
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GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
ExAC
?
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1
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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 submitter | clinical testing | Ambry Genetics | Aug 28, 2023 | The c.322A>G (p.T108A) alteration is located in exon 1 (coding exon 1) of the WDR36 gene. This alteration results from a A to G substitution at nucleotide position 322, causing the threonine (T) at amino acid position 108 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
Cadd
Pathogenic
Dann
Uncertain
DEOGEN2
Benign
T;T;T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
M_CAP
Benign
T
MetaRNN
Uncertain
D;D;D
MetaSVM
Benign
T
MutationAssessor
Benign
L;L;.
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;.;.
REVEL
Uncertain
Sift4G
Benign
T;T;T
Polyphen
D;D;.
Vest4
MutPred
Gain of catalytic residue at T108 (P = 0.0608);Gain of catalytic residue at T108 (P = 0.0608);.;
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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Calibrated prediction
Score
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at