Variant rs144081442 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2

The NM_001029896.2(WDR45):c.398G>A(p.Arg133Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000019 in 1,210,487 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 6 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., 1 hem., cov: 23)

Exomes 𝑓: 0.000015 ( 0 hom. 5 hem. )

Consequence

WDR45
NM_001029896.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.779

Variant links:

Genes affected

WDR45 (HGNC:28912): (WD repeat domain 45) 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. This gene has a pseudogene at chromosome 4q31.3. Multiple alternatively spliced transcript variants encoding distinct isoforms have been found for this gene, but the biological validity and full-length nature of some variants have not been determined. [provided by RefSeq, Jul 2008]

WDR45 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.08614415).

BP6

Variant X-49076468-C-T is Benign according to our data. Variant chrX-49076468-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 583164.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAdExome4 at 5 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR45	NM_001029896.2 linkuse as main transcript	c.398G>A	p.Arg133Gln	missense_variant	6/11	ENST00000376372.9	NP_001025067.1
WDR45	NM_007075.4 linkuse as main transcript	c.401G>A	p.Arg134Gln	missense_variant	7/12		NP_009006.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDR45	ENST00000376372.9 linkuse as main transcript	c.398G>A	p.Arg133Gln	missense_variant	6/11	1	NM_001029896.2	ENSP00000365551	P4	Q9Y484-1

Frequencies

GnomAD3 genomes

AF:

0.0000534

AC:

AN:

112362

Hom.:

Cov.:

AF XY:

0.0000290

AC XY:

AN XY:

34520

show subpopulations

Gnomad AFR

AF:

0.000129

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000376

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000545

AC:

AN:

183450

Hom.:

AF XY:

0.00

AC XY:

AN XY:

67898

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000122

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000155

AC:

AN:

1098125

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

363513

show subpopulations

Gnomad4 AFR exome

AF:

0.0000379

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000185

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000154

Gnomad4 OTH exome

AF:

0.0000434

GnomAD4 genome

AF:

0.0000534

AC:

AN:

112362

Hom.:

Cov.:

AF XY:

0.0000290

AC XY:

AN XY:

34520

show subpopulations

Gnomad4 AFR

AF:

0.000129

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000376

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000453

ESP6500AA

AF:

0.000261

AC:

ESP6500EA

AF:

0.000149

AC:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Neurodegeneration with brain iron accumulation 5

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Sep 04, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Benign

0.89

DEOGEN2

Benign

0.021

T;T;.;.;.;.;T;.;T;T;T;.;T;T;.;.;T;T

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.86

.;D;D;D;.;D;D;D;D;D;T;D;D;D;D;D;D;D

M_CAP

Benign

0.013

MetaRNN

Benign

0.086

T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.38

N;N;.;N;.;.;.;.;.;.;.;.;.;.;.;.;.;.

MutationTaster

Benign

1.0

N;N;N;N;N;N;N;N

PrimateAI

Benign

0.43

PROVEAN

Benign

0.36

N;.;.;N;N;N;N;N;.;.;N;.;N;.;.;N;N;.

REVEL

Benign

0.19

Sift

Benign

1.0

T;.;.;T;T;T;T;T;.;.;T;.;T;.;.;T;T;.

Sift4G

Benign

0.89

T;T;T;T;T;T;T;T;T;.;.;.;.;.;T;.;.;.

Polyphen

0.0

B;B;.;B;B;B;B;B;.;.;.;.;.;.;.;.;.;.

Vest4

0.15

MVP

0.35

MPC

0.70

ClinPred

0.068

GERP RS

4.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.097

gMVP

0.18

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