Variant chr17-82630999-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_019613.4(WDR45B):c.166C>G(p.His56Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,461,634 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

WDR45B
NM_019613.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.56

Variant links:

Genes affected

WDR45B (HGNC:25072): (WD repeat domain 45B) This gene encodes a member of the WIPI or SVP1 family of WD40 repeat-containing proteins. The protein contains seven WD40 repeats that are thought to fold into a beta-propeller structure that mediates protein-protein interactions, and a conserved motif for interaction with phospholipids. The human genome contains several pseudogenes of this gene. [provided by RefSeq, Jul 2008]

WDR45B links:

WDR45B (HGNC:):

WDR45B links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR45B	NM_019613.4 linkuse as main transcript	c.166C>G	p.His56Asp	missense_variant	3/10	ENST00000392325.9	NP_062559.2	Q5MNZ6
WDR45B	XM_047436414.1 linkuse as main transcript	c.166C>G	p.His56Asp	missense_variant	3/7		XP_047292370.1
WDR45B	XM_005256377.6 linkuse as main transcript	c.143-3708C>G		intron_variant			XP_005256434.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDR45B	ENST00000392325.9 linkuse as main transcript	c.166C>G	p.His56Asp	missense_variant	3/10	1	NM_019613.4	ENSP00000376139.4		Q5MNZ6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000119

AC:

AN:

251434

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135892

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000547

AC:

AN:

1461634

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727130

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000151

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 29, 2024

The c.166C>G (p.H56D) alteration is located in exon 3 (coding exon 3) of the WDR45B gene. This alteration results from a C to G substitution at nucleotide position 166, causing the histidine (H) at amino acid position 56 to be replaced by an aspartic acid (D). 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

Pathogenic

0.64

BayesDel_addAF

Uncertain

0.16

BayesDel_noAF

Pathogenic

0.22

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.24

Eigen

Uncertain

0.45

Eigen_PC

Uncertain

0.51

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.95

M_CAP

Benign

0.048

MetaRNN

Uncertain

0.74

MetaSVM

Benign

-0.51

MutationAssessor

Uncertain

2.8

PrimateAI

Pathogenic

0.83

PROVEAN

Uncertain

-3.8

REVEL

Uncertain

0.47

Sift

Benign

0.19

Sift4G

Benign

0.20

Polyphen

0.51

Vest4

0.84

MutPred

0.57

Loss of sheet (P = 0.1501);

MVP

0.79

MPC

0.83

ClinPred

0.75

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.77

gMVP

0.80

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