Variant rs201384117 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001029896.2(WDR45):c.437-27A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000036 in 1,140,106 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., 2 hem., cov: 23)

Exomes 𝑓: 0.000037 ( 0 hom. 13 hem. )

Consequence

WDR45
NM_001029896.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.230

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:

ENSG00000288053 (HGNC:):

ENSG00000288053 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

This place is a probable branch point but likely benign (scored 1 / 10). Computational evidence support a benign effect (MetaRNN=0.032790303).

BS2

High Hemizygotes in GnomAd4 at 2 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR45	NM_001029896.2 linkuse as main transcript	c.437-27A>T		intron_variant		ENST00000376372.9	NP_001025067.1	Q9Y484-1A0A024QYX1
WDR45	NM_007075.4 linkuse as main transcript	c.440-27A>T		intron_variant			NP_009006.2	Q9Y484-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDR45	ENST00000376372.9 linkuse as main transcript	c.437-27A>T		intron_variant		1	NM_001029896.2	ENSP00000365551.3		Q9Y484-1
ENSG00000288053	ENST00000376358.4 linkuse as main transcript	c.131-27A>T		intron_variant		2		ENSP00000365536.3		A6NM71

Frequencies

GnomAD3 genomes

AF:

0.0000275

AC:

AN:

109261

Hom.:

Cov.:

AF XY:

0.0000627

AC XY:

AN XY:

31903

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.000173

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000191

Gnomad OTH

AF:

0.000680

GnomAD3 exomes

AF:

0.0000555

AC:

AN:

162303

Hom.:

AF XY:

0.0000588

AC XY:

AN XY:

51035

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:

0.000407

Gnomad NFE exome

AF:

0.0000287

Gnomad OTH exome

AF:

0.000243

GnomAD4 exome

AF:

0.0000369

AC:

AN:

1030845

Hom.:

Cov.:

AF XY:

0.0000424

AC XY:

AN XY:

306383

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000802

Gnomad4 NFE exome

AF:

0.00000637

Gnomad4 OTH exome

AF:

0.0000228

GnomAD4 genome

AF:

0.0000275

AC:

AN:

109261

Hom.:

Cov.:

AF XY:

0.0000627

AC XY:

AN XY:

31903

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000173

Gnomad4 NFE

AF:

0.0000191

Gnomad4 OTH

AF:

0.000680

Alfa

AF:

0.000198

Hom.:

ExAC

AF:

0.0000661

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.81

CADD

Benign

1.6

DANN

Benign

0.76

DEOGEN2

Benign

0.0020

.;.;T

FATHMM_MKL

Benign

0.076

LIST_S2

Benign

0.17

T;T;T

M_CAP

Benign

0.0086

MetaRNN

Benign

0.033

T;T;T

MetaSVM

Benign

-1.0

PROVEAN

Benign

0.15

N;N;N

REVEL

Benign

0.011

Sift

Benign

0.65

T;T;T

Sift4G

Benign

0.75

T;.;.

Vest4

0.23

MutPred

0.40

Loss of ubiquitination at K145 (P = 0.0508);.;Loss of ubiquitination at K145 (P = 0.0508);

MVP

0.18

ClinPred

0.0071

GERP RS

-2.3

BranchPoint Hunter

1.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over