Variant X-48604318-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP2BP4_ModerateBS2

The NM_001347217.2(WDR13):c.1201A>G(p.Ile401Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000397 in 1,209,734 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 15 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 0.000045 ( 0 hom., 3 hem., cov: 23)

Exomes 𝑓: 0.000039 ( 0 hom. 12 hem. )

Consequence

WDR13
NM_001347217.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.61

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]

WDR13 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), WDR13. . Gene score misZ 3.2948 (greater than the threshold 3.09). GenCC has associacion of gene with intellectual disability.

BP4

Computational evidence support a benign effect (MetaRNN=0.09067017).

BS2

High Hemizygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR13	NM_001347217.2 linkuse as main transcript	c.1201A>G	p.Ile401Val	missense_variant	9/10	ENST00000376729.10	NP_001334146.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDR13	ENST00000376729.10 linkuse as main transcript	c.1201A>G	p.Ile401Val	missense_variant	9/10	5	NM_001347217.2	ENSP00000365919	P1

Frequencies

GnomAD3 genomes

AF:

0.0000446

AC:

AN:

112131

Hom.:

Cov.:

AF XY:

0.0000875

AC XY:

AN XY:

34295

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000946

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:

0.0000753

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000553

AC:

AN:

180710

Hom.:

AF XY:

0.0000306

AC XY:

AN XY:

65318

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000147

Gnomad ASJ exome

AF:

0.000135

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000496

Gnomad OTH exome

AF:

0.000224

GnomAD4 exome

AF:

0.0000392

AC:

AN:

1097549

Hom.:

Cov.:

AF XY:

0.0000331

AC XY:

AN XY:

362921

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000142

Gnomad4 ASJ exome

AF:

0.0000516

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000404

Gnomad4 OTH exome

AF:

0.0000651

GnomAD4 genome

AF:

0.0000446

AC:

AN:

112185

Hom.:

Cov.:

AF XY:

0.0000873

AC XY:

AN XY:

34359

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000944

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000753

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000217

Hom.:

Bravo

AF:

0.0000567

ExAC

AF:

0.0000330

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 25, 2023

The c.1201A>G (p.I401V) alteration is located in exon 8 (coding exon 8) of the WDR13 gene. This alteration results from a A to G substitution at nucleotide position 1201, causing the isoleucine (I) at amino acid position 401 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

0.061

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0096

.;.;T

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.79

.;.;T

M_CAP

Uncertain

0.25

MetaRNN

Benign

0.091

T;T;T

MetaSVM

Benign

-0.95

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-0.36

N;N;.

REVEL

Benign

0.15

Sift

Benign

0.35

T;T;.

Sift4G

Benign

0.36

T;T;T

Vest4

0.22

MutPred

0.60

Gain of ubiquitination at K396 (P = 0.0913);Gain of ubiquitination at K396 (P = 0.0913);.;

MVP

0.40

MPC

0.88

ClinPred

0.062

GERP RS

5.7

gMVP

0.47

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over