Variant chrX-118392650-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_019045.5(WDR44):c.205G>C(p.Glu69Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000923 in 1,083,146 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 23)

Exomes 𝑓: 9.2e-7 ( 0 hom. 0 hem. )

Consequence

WDR44
NM_019045.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.71

Variant links:

Genes affected

WDR44 (HGNC:30512): (WD repeat domain 44) This gene encodes a protein that interacts with the small GTPase rab11. A similar protein in rat binds the GTP-containing active form of rab11. This protein may play a role in endosome recycling. Alternate splicing results in multiple transcript variants.[provided by RefSeq, May 2010]

WDR44 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.37016478).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
WDR44	NM_019045.5 linkuse as main transcript	c.205G>C	p.Glu69Gln	missense_variant	4/20	ENST00000254029.8
WDR44	NM_001184965.2 linkuse as main transcript	c.205G>C	p.Glu69Gln	missense_variant	4/20
WDR44	NM_001184966.1 linkuse as main transcript	c.130G>C	p.Glu44Gln	missense_variant	3/18
WDR44	XM_011531353.4 linkuse as main transcript	c.130G>C	p.Glu44Gln	missense_variant	3/19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WDR44	ENST00000254029.8 linkuse as main transcript	c.205G>C	p.Glu69Gln	missense_variant	4/20	1	NM_019045.5	P1	Q5JSH3-1
WDR44	ENST00000371825.7 linkuse as main transcript	c.205G>C	p.Glu69Gln	missense_variant	4/20	1			Q5JSH3-2
WDR44	ENST00000371822.9 linkuse as main transcript	c.130G>C	p.Glu44Gln	missense_variant	3/18	2			Q5JSH3-4
WDR44	ENST00000493448.1 linkuse as main transcript	n.476G>C		non_coding_transcript_exon_variant	3/3	4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000117

AC:

AN:

170984

Hom.:

AF XY:

0.00

AC XY:

AN XY:

58672

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000814

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

9.23e-7

AC:

AN:

1083146

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

352322

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000305

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000330

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

Apr 14, 2022

The c.205G>C (p.E69Q) alteration is located in exon 4 (coding exon 4) of the WDR44 gene. This alteration results from a G to C substitution at nucleotide position 205, causing the glutamic acid (E) at amino acid position 69 to be replaced by a glutamine (Q). 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

Benign

0.13

BayesDel_addAF

Benign

-0.069

BayesDel_noAF

Benign

-0.14

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.25

.;T;.

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Benign

0.85

T;D;D

M_CAP

Pathogenic

0.61

MetaRNN

Benign

0.37

T;T;T

MetaSVM

Uncertain

0.0058

MutationAssessor

Benign

1.8

.;L;L

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-0.88

N;N;N

REVEL

Benign

0.29

Sift

Pathogenic

0.0

D;D;D

Sift4G

Benign

0.12

T;T;T

Polyphen

1.0, 1.0

.;D;D

Vest4

0.42

MutPred

0.24

.;Gain of methylation at K73 (P = 0.1201);Gain of methylation at K73 (P = 0.1201);

MVP

0.75

MPC

0.78

ClinPred

0.45

GERP RS

5.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.63

gMVP

0.25

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