Variant chrX-48599387-G-A details in Genebe, Genetics Data Aggregator

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

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]

WDR13 links:

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
WDR13	NM_001347217.2 link	c.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
WDR13	ENST00000376729.10 link	c.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:

AN:

113076

Hom.:

Cov.:

AF XY:

0.00

AC XY:

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:

AN:

172703

Hom.:

AF XY:

0.00

AC XY:

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:

AN:

1093942

Hom.:

Cov.:

AF XY:

0.0000278

AC XY:

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:

AN:

113076

Hom.:

Cov.:

AF XY:

0.00

AC XY:

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:

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

BayesDel_noAF

Uncertain

-0.040

CADD

Uncertain

DANN

Pathogenic

1.0

FATHMM_MKL

Pathogenic

0.98

M_CAP

Uncertain

0.17

MetaRNN

Benign

0.29

T;T

MetaSVM

Uncertain

-0.27

PrimateAI

Uncertain

0.78

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

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.

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