Variant 2-28894805-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_015131.3(WDR43):c.107G>A(p.Gly36Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,458,564 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

WDR43
NM_015131.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.20

Variant links:

Genes affected

WDR43 (HGNC:28945): (WD repeat domain 43) Enables RNA binding activity. Involved in positive regulation of rRNA processing and positive regulation of transcription by RNA polymerase I. Located in fibrillar center. [provided by Alliance of Genome Resources, Apr 2022]

WDR43 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.892

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR43	NM_015131.3 linkuse as main transcript	c.107G>A	p.Gly36Asp	missense_variant	1/18	ENST00000407426.8	NP_055946.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDR43	ENST00000407426.8 linkuse as main transcript	c.107G>A	p.Gly36Asp	missense_variant	1/18	1	NM_015131.3	ENSP00000384302	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000826

AC:

AN:

242144

Hom.:

AF XY:

0.00000757

AC XY:

AN XY:

132044

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:

0.0000183

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1458564

Hom.:

Cov.:

AF XY:

0.00000414

AC XY:

AN XY:

725364

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:

0.0000117

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000166

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 19, 2023

The c.107G>A (p.G36D) alteration is located in exon 1 (coding exon 1) of the WDR43 gene. This alteration results from a G to A substitution at nucleotide position 107, causing the glycine (G) at amino acid position 36 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

0.99

BayesDel_addAF

Pathogenic

0.39

BayesDel_noAF

Pathogenic

0.32

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.25

Eigen

Pathogenic

0.73

Eigen_PC

Uncertain

0.64

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.78

M_CAP

Pathogenic

0.51

MetaRNN

Pathogenic

0.89

MetaSVM

Uncertain

0.17

MutationAssessor

Uncertain

2.9

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.90

PROVEAN

Pathogenic

-5.5

REVEL

Pathogenic

0.71

Sift

Uncertain

0.0050

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.94

MutPred

0.55

Gain of sheet (P = 0.1451);

MVP

0.75

MPC

0.76

ClinPred

0.99

GERP RS

4.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Varity_R

0.79

gMVP

0.72

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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