rs782723344

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_001347217.2(WDR13):​c.317G>A​(p.Arg106His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000249 in 1,207,018 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 10 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000044 ( 0 hom., 0 hem., cov: 25)
Exomes 𝑓: 0.000023 ( 0 hom. 10 hem. )

Consequence

WDR13
NM_001347217.2 missense

Scores

2
8
4

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.73
Variant links:
Genes affected
WDR13 (HGNC:14352): (WD repeat domain 13) 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. A similar protein in mouse is thought to be a negative regulator of the pancreatic beta cell proliferation. Mice lacking this gene exhibit increased pancreatic islet mass and higher serum insulin levels, and are mildly obese. [provided by RefSeq, Nov 2016]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.29497552).
BS2
High Hemizygotes in GnomAdExome4 at 10 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
WDR13NM_001347217.2 linkc.317G>A p.Arg106His missense_variant Exon 4 of 10 ENST00000376729.10 NP_001334146.1 Q9H1Z4-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
WDR13ENST00000376729.10 linkc.317G>A p.Arg106His missense_variant Exon 4 of 10 5 NM_001347217.2 ENSP00000365919.5 Q9H1Z4-1

Frequencies

GnomAD3 genomes
AF:
0.0000442
AC:
5
AN:
113076
Hom.:
0
Cov.:
25
AF XY:
0.00
AC XY:
0
AN XY:
35204
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000278
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000278
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000188
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000290
AC:
5
AN:
172703
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
59223
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000386
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.0000659
Gnomad NFE exome
AF:
0.0000389
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000229
AC:
25
AN:
1093942
Hom.:
0
Cov.:
31
AF XY:
0.0000278
AC XY:
10
AN XY:
360072
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000291
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000199
Gnomad4 SAS exome
AF:
0.0000187
Gnomad4 FIN exome
AF:
0.000124
Gnomad4 NFE exome
AF:
0.0000131
Gnomad4 OTH exome
AF:
0.0000218
GnomAD4 genome
AF:
0.0000442
AC:
5
AN:
113076
Hom.:
0
Cov.:
25
AF XY:
0.00
AC XY:
0
AN XY:
35204
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000278
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000278
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000188
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000340
ExAC
AF:
0.0000247
AC:
3

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Aug 28, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.317G>A (p.R106H) alteration is located in exon 3 (coding exon 3) of the WDR13 gene. This alteration results from a G to A substitution at nucleotide position 317, causing the arginine (R) at amino acid position 106 to be replaced by a histidine (H). 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
Uncertain
0.45
BayesDel_addAF
Uncertain
0.14
D
BayesDel_noAF
Uncertain
-0.040
CADD
Uncertain
25
DANN
Pathogenic
1.0
FATHMM_MKL
Pathogenic
0.98
D
M_CAP
Uncertain
0.17
D
MetaRNN
Benign
0.29
T;T
MetaSVM
Uncertain
-0.27
T
PrimateAI
Uncertain
0.78
T
PROVEAN
Benign
-1.4
N;N
REVEL
Uncertain
0.44
Sift
Benign
0.039
D;D
Sift4G
Uncertain
0.038
D;D
Vest4
0.49
MutPred
0.44
Loss of methylation at R106 (P = 0.0117);Loss of methylation at R106 (P = 0.0117);
MVP
0.59
MPC
2.0
ClinPred
0.42
T
GERP RS
5.1
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
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: rs782723344; hg19: chrX-48457775; COSMIC: COSV54333562; COSMIC: COSV54333562; API