chr5-111092571-C-G

Variant summary

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

The NM_139281.3(WDR36):ā€‹c.115C>Gā€‹(p.Arg39Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000328 in 1,614,122 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: š‘“ 0.000020 ( 0 hom., cov: 33)
Exomes š‘“: 0.000034 ( 0 hom. )

Consequence

WDR36
NM_139281.3 missense

Scores

4
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.848
Variant links:
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 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.21717969).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
WDR36NM_139281.3 linkc.115C>G p.Arg39Gly missense_variant Exon 1 of 23 ENST00000513710.4 NP_644810.2 Q8NI36
WDR36XM_047416729.1 linkc.115C>G p.Arg39Gly missense_variant Exon 1 of 21 XP_047272685.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
WDR36ENST00000513710.4 linkc.115C>G p.Arg39Gly missense_variant Exon 1 of 23 1 NM_139281.3 ENSP00000424628.3 A0A0A0MTB8
WDR36ENST00000505303.5 linkn.251C>G non_coding_transcript_exon_variant Exon 1 of 15 5
WDR36ENST00000515784.1 linkn.225C>G non_coding_transcript_exon_variant Exon 1 of 2 2

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152242
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000482
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000924
AC:
23
AN:
249020
Hom.:
0
AF XY:
0.0000817
AC XY:
11
AN XY:
134678
show subpopulations
Gnomad AFR exome
AF:
0.0000622
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000272
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000143
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000342
AC:
50
AN:
1461762
Hom.:
0
Cov.:
31
AF XY:
0.0000316
AC XY:
23
AN XY:
727172
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:
0.0000116
Gnomad4 FIN exome
AF:
0.0000375
Gnomad4 NFE exome
AF:
0.0000342
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152360
Hom.:
0
Cov.:
33
AF XY:
0.0000134
AC XY:
1
AN XY:
74512
show subpopulations
Gnomad4 AFR
AF:
0.0000481
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000434
Hom.:
0
Bravo
AF:
0.0000227
ExAC
AF:
0.000148
AC:
18
EpiCase
AF:
0.0000545
EpiControl
AF:
0.0000593

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Uncertain:1
Sep 23, 2022
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 95 of the WDR36 protein (p.Arg95Gly). This variant is present in population databases (rs772030651, gnomAD 0.03%). This missense change has been observed in individual(s) with glaucoma (PMID: 24825108, 32476818). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.26
BayesDel_addAF
Benign
-0.31
T
BayesDel_noAF
Benign
-0.38
CADD
Benign
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.12
T;T;T
Eigen
Benign
0.14
Eigen_PC
Uncertain
0.31
FATHMM_MKL
Uncertain
0.78
D
LIST_S2
Benign
0.76
.;T;T
M_CAP
Benign
0.0066
T
MetaRNN
Benign
0.22
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.81
L;L;.
PrimateAI
Uncertain
0.53
T
PROVEAN
Benign
-0.90
N;.;.
REVEL
Benign
0.14
Sift4G
Benign
0.085
T;T;T
Polyphen
0.53
P;P;.
Vest4
0.46
MutPred
0.59
Loss of stability (P = 0.0181);Loss of stability (P = 0.0181);.;
MVP
0.49
MPC
0.037
ClinPred
0.33
T
GERP RS
5.0
Varity_R
0.63
gMVP
0.60

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: rs772030651; hg19: chr5-110428269; COSMIC: COSV72411394; COSMIC: COSV72411394; API