NM_001347217.2:c.748C>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001347217.2(WDR13):​c.748C>T​(p.Arg250Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000578 in 1,210,569 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000089 ( 0 hom., 0 hem., cov: 25)
Exomes 𝑓: 0.0000055 ( 0 hom. 1 hem. )

Consequence

WDR13
NM_001347217.2 missense

Scores

7
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.18
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 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 rank MANE Protein UniProt
WDR13NM_001347217.2 linkc.748C>T p.Arg250Cys missense_variant Exon 6 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.748C>T p.Arg250Cys missense_variant Exon 6 of 10 5 NM_001347217.2 ENSP00000365919.5 Q9H1Z4-1

Frequencies

GnomAD3 genomes
AF:
0.00000887
AC:
1
AN:
112739
Hom.:
0
Cov.:
25
AF XY:
0.00
AC XY:
0
AN XY:
34891
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:
0.0000188
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000549
AC:
1
AN:
182216
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
66808
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:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000123
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000547
AC:
6
AN:
1097830
Hom.:
0
Cov.:
31
AF XY:
0.00000275
AC XY:
1
AN XY:
363204
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:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000713
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000887
AC:
1
AN:
112739
Hom.:
0
Cov.:
25
AF XY:
0.00
AC XY:
0
AN XY:
34891
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:
0.0000188
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000113
EpiCase
AF:
0.00
EpiControl
AF:
0.0000595

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Dec 04, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.748C>T (p.R250C) alteration is located in exon 5 (coding exon 5) of the WDR13 gene. This alteration results from a C to T substitution at nucleotide position 748, causing the arginine (R) at amino acid position 250 to be replaced by a cysteine (C). 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
Benign
0.14
BayesDel_addAF
Uncertain
0.084
D
BayesDel_noAF
Benign
-0.12
CADD
Uncertain
23
DANN
Uncertain
1.0
FATHMM_MKL
Uncertain
0.94
D
M_CAP
Uncertain
0.11
D
MetaRNN
Uncertain
0.44
T;T
MetaSVM
Benign
-0.75
T
PrimateAI
Uncertain
0.67
T
PROVEAN
Benign
-1.9
N;N
REVEL
Uncertain
0.33
Sift
Benign
0.10
T;T
Sift4G
Benign
0.093
T;T
Vest4
0.44
MutPred
0.56
Loss of disorder (P = 0.0474);Loss of disorder (P = 0.0474);
MVP
0.62
MPC
1.3
ClinPred
0.78
D
GERP RS
4.2
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
gMVP
0.68

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: rs888327763; hg19: chrX-48458931; API