X-48601914-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001347217.2(WDR13):​c.962C>T​(p.Ala321Val) variant causes a missense change. The variant allele was found at a frequency of 0.00001 in 1,198,367 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 5 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., 0 hem., cov: 24)
Exomes 𝑓: 0.0000083 ( 0 hom. 5 hem. )

Consequence

WDR13
NM_001347217.2 missense

Scores

8
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:3

Conservation

PhyloP100: 6.84
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 -4 ACMG points.

BS2
High Hemizygotes in GnomAdExome4 at 5 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
WDR13NM_001347217.2 linkc.962C>T p.Ala321Val missense_variant Exon 7 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.962C>T p.Ala321Val missense_variant Exon 7 of 10 5 NM_001347217.2 ENSP00000365919.5 Q9H1Z4-1
WDR13ENST00000218056.9 linkc.962C>T p.Ala321Val missense_variant Exon 6 of 9 1 ENSP00000218056.5 Q9H1Z4-1
WDR13ENST00000479279.5 linkn.1829C>T non_coding_transcript_exon_variant Exon 5 of 8 1
WDR13ENST00000482760.3 linkc.206C>T p.Ala69Val missense_variant Exon 2 of 5 3 ENSP00000483191.1 A0A087X091

Frequencies

GnomAD3 genomes
AF:
0.0000266
AC:
3
AN:
112698
Hom.:
0
Cov.:
24
AF XY:
0.00
AC XY:
0
AN XY:
34840
show subpopulations
Gnomad AFR
AF:
0.0000322
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000187
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000829
AC:
9
AN:
1085669
Hom.:
0
Cov.:
31
AF XY:
0.0000142
AC XY:
5
AN XY:
353061
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000293
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:
0.00000719
Gnomad4 OTH exome
AF:
0.0000439
GnomAD4 genome
AF:
0.0000266
AC:
3
AN:
112698
Hom.:
0
Cov.:
24
AF XY:
0.00
AC XY:
0
AN XY:
34840
show subpopulations
Gnomad4 AFR
AF:
0.0000322
Gnomad4 AMR
AF:
0.000187
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000718

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:3
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Uncertain:2
-
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+
Significance: Uncertain significance
Review Status: no assertion criteria provided
Collection Method: clinical testing

- -

-
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Significance: Uncertain significance
Review Status: no assertion criteria provided
Collection Method: clinical testing

- -

not specified Uncertain:1
May 17, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.962C>T (p.A321V) alteration is located in exon 6 (coding exon 6) of the WDR13 gene. This alteration results from a C to T substitution at nucleotide position 962, causing the alanine (A) at amino acid position 321 to be replaced by a valine (V). 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
0.28
BayesDel_addAF
Uncertain
0.15
D
BayesDel_noAF
Uncertain
-0.020
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.036
.;.;T
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Uncertain
0.96
.;.;D
M_CAP
Benign
0.081
D
MetaRNN
Uncertain
0.61
D;D;D
MetaSVM
Benign
-0.73
T
PrimateAI
Uncertain
0.76
T
PROVEAN
Benign
-1.8
N;N;.
REVEL
Uncertain
0.35
Sift
Benign
0.23
T;T;.
Sift4G
Benign
0.27
T;T;T
Vest4
0.80
MutPred
0.56
Loss of catalytic residue at A321 (P = 0.0396);Loss of catalytic residue at A321 (P = 0.0396);.;
MVP
0.73
MPC
1.1
ClinPred
0.92
D
GERP RS
5.4
gMVP
0.90

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.33
Details are displayed if max score is > 0.2
DS_DG_spliceai
0.33
Position offset: -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: rs1163033477; hg19: chrX-48460302; COSMIC: COSV54331692; COSMIC: COSV54331692; API