Genetic Variant WDR13:p.Arg32His (chrX-48598770-G-A) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_001347217.2(WDR13):c.95G>A(p.Arg32His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R32L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 23)

Consequence

WDR13
NM_001347217.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 8.89

Publications

1 publications found

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 Gene-Disease associations (from GenCC):

intellectual disability
Inheritance: XL Classification: LIMITED Submitted by: Ambry Genetics

WDR13 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.786

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001347217.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
WDR13	NM_001347217.2	MANE Select	c.95G>A	p.Arg32His	missense	Exon 3 of 10	NP_001334146.1	Q9H1Z4-1
WDR13	NM_017883.6		c.95G>A	p.Arg32His	missense	Exon 2 of 9	NP_060353.2
WDR13	NM_001166426.3		c.-182G>A		5_prime_UTR	Exon 1 of 8	NP_001159898.1	Q9H1Z4-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
WDR13	ENST00000376729.10	TSL:5 MANE Select	c.95G>A	p.Arg32His	missense	Exon 3 of 10	ENSP00000365919.5	Q9H1Z4-1
WDR13	ENST00000218056.9	TSL:1	c.95G>A	p.Arg32His	missense	Exon 2 of 9	ENSP00000218056.5	Q9H1Z4-1
WDR13	ENST00000479279.5	TSL:1	n.962G>A		non_coding_transcript_exon	Exon 1 of 8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.98

BayesDel_addAF

Pathogenic

0.18

BayesDel_noAF

Uncertain

0.020

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.26

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.97

M_CAP

Uncertain

0.18

MetaRNN

Pathogenic

0.79

MetaSVM

Uncertain

0.19

PhyloP100

8.9

PrimateAI

Pathogenic

0.85

PROVEAN

Uncertain

-3.8

REVEL

Pathogenic

0.66

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.0050

Vest4

0.59

MutPred

0.55

Loss of MoRF binding (P = 0.0504)

MVP

0.88

MPC

2.4

ClinPred

0.99

GERP RS

4.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

gMVP

0.97

Mutation Taster

=81/19

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over