5-111092531-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_139281.3(WDR36):ā€‹c.75C>Gā€‹(p.Asn25Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000142 in 1,614,108 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‘“ 0.0000066 ( 0 hom., cov: 33)
Exomes š‘“: 0.000015 ( 0 hom. )

Consequence

WDR36
NM_139281.3 missense

Scores

2
4
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0390
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.37309188).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
WDR36NM_139281.3 linkc.75C>G p.Asn25Lys missense_variant Exon 1 of 23 ENST00000513710.4 NP_644810.2 Q8NI36
WDR36XM_047416729.1 linkc.75C>G p.Asn25Lys 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.75C>G p.Asn25Lys missense_variant Exon 1 of 23 1 NM_139281.3 ENSP00000424628.3 A0A0A0MTB8
WDR36ENST00000505303.5 linkn.211C>G non_coding_transcript_exon_variant Exon 1 of 15 5
WDR36ENST00000515784.1 linkn.185C>G non_coding_transcript_exon_variant Exon 1 of 2 2

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152248
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000399
AC:
1
AN:
250592
Hom.:
0
AF XY:
0.00000738
AC XY:
1
AN XY:
135508
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000150
AC:
22
AN:
1461860
Hom.:
0
Cov.:
31
AF XY:
0.0000124
AC XY:
9
AN XY:
727224
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:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000180
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152248
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
74386
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000225
Hom.:
0
Bravo
AF:
0.00000756
ExAC
AF:
0.00000824
AC:
1

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Nov 10, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.243C>G (p.N81K) alteration is located in exon 1 (coding exon 1) of the WDR36 gene. This alteration results from a C to G substitution at nucleotide position 243, causing the asparagine (N) at amino acid position 81 to be replaced by a lysine (K). 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
Pathogenic
0.61
BayesDel_addAF
Benign
-0.20
T
BayesDel_noAF
Benign
-0.43
CADD
Benign
16
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.43
T;T;T
Eigen
Benign
-0.24
Eigen_PC
Benign
-0.26
FATHMM_MKL
Uncertain
0.83
D
LIST_S2
Benign
0.71
.;T;T
M_CAP
Benign
0.029
D
MetaRNN
Benign
0.37
T;T;T
MetaSVM
Benign
-0.70
T
MutationAssessor
Benign
1.6
L;L;.
PrimateAI
Benign
0.46
T
PROVEAN
Pathogenic
-4.6
D;.;.
REVEL
Benign
0.19
Sift4G
Uncertain
0.011
D;D;D
Polyphen
0.43
B;B;.
Vest4
0.36
MutPred
0.55
Gain of MoRF binding (P = 0.0254);Gain of MoRF binding (P = 0.0254);.;
MVP
0.82
MPC
0.050
ClinPred
0.98
D
GERP RS
2.3
Varity_R
0.62
gMVP
0.67

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: rs149994285; hg19: chr5-110428229; API