X-48601934-G-A

Position:

chrX-48601934-G-A

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 1P and 10B. PP2BP4_StrongBP6_ModerateBS2

The NM_001347217.2(WDR13):c.982G>A(p.Val328Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000753 in 1,194,775 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 281 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00079 ( 0 hom., 29 hem., cov: 24)

Exomes 𝑓: 0.00075 ( 0 hom. 252 hem. )

Consequence

WDR13
NM_001347217.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:3

Conservation

PhyloP100: 1.99

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 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=0.011793971).

BP6

Variant X-48601934-G-A is Benign according to our data. Variant chrX-48601934-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 715468.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-48601934-G-A is described in Lovd as [Likely_benign].

BS2

High Hemizygotes in GnomAd4 at 29 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR13	NM_001347217.2 linkuse as main transcript	c.982G>A	p.Val328Ile	missense_variant	7/10	ENST00000376729.10	NP_001334146.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
WDR13	ENST00000376729.10 linkuse as main transcript	c.982G>A	p.Val328Ile	missense_variant	7/10	5	NM_001347217.2	ENSP00000365919	P1
WDR13	ENST00000218056.9 linkuse as main transcript	c.982G>A	p.Val328Ile	missense_variant	6/9	1		ENSP00000218056	P1
WDR13	ENST00000479279.5 linkuse as main transcript	n.1849G>A		non_coding_transcript_exon_variant	5/8	1
WDR13	ENST00000482760.3 linkuse as main transcript	c.226G>A	p.Val76Ile	missense_variant	2/5	3		ENSP00000483191

Frequencies

GnomAD3 genomes

AF:

0.000798

AC:

AN:

112719

Hom.:

Cov.:

AF XY:

0.000832

AC XY:

AN XY:

34861

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00112

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000361

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00837

Gnomad NFE

AF:

0.00135

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000674

AC:

114

AN:

169097

Hom.:

AF XY:

0.000675

AC XY:

AN XY:

56307

show subpopulations

Gnomad AFR exome

AF:

0.0000767

Gnomad AMR exome

AF:

0.00105

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000191

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00106

Gnomad OTH exome

AF:

0.000729

GnomAD4 exome

AF:

0.000750

AC:

811

AN:

1082003

Hom.:

Cov.:

AF XY:

0.000718

AC XY:

252

AN XY:

350859

show subpopulations

Gnomad4 AFR exome

AF:

0.000115

Gnomad4 AMR exome

AF:

0.00106

Gnomad4 ASJ exome

AF:

0.0000544

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000503

Gnomad4 FIN exome

AF:

0.0000250

Gnomad4 NFE exome

AF:

0.000849

Gnomad4 OTH exome

AF:

0.000706

GnomAD4 genome

AF:

0.000789

AC:

AN:

112772

Hom.:

Cov.:

AF XY:

0.000830

AC XY:

AN XY:

34924

show subpopulations

Gnomad4 AFR

AF:

0.0000962

Gnomad4 AMR

AF:

0.00112

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00135

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00140

Hom.:

Bravo

AF:

0.000774

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00149

AC:

ExAC

AF:

0.000528

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Aug 16, 2017	- -
Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.64

CADD

Benign

8.6

DANN

Benign

0.26

DEOGEN2

Benign

0.013

.;.;T

FATHMM_MKL

Uncertain

0.77

LIST_S2

Benign

0.81

.;.;T

M_CAP

Benign

0.017

MetaRNN

Benign

0.012

T;T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

0.98

N;N

PrimateAI

Uncertain

0.49

PROVEAN

Benign

0.64

N;N;.

REVEL

Benign

0.066

Sift

Benign

1.0

T;T;.

Sift4G

Benign

1.0

T;T;T

Vest4

0.084

MVP

0.12

MPC

0.83

ClinPred

0.0049

GERP RS

3.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

gMVP

0.33

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