Variant X-118392856-A-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_019045.5(WDR44):c.411A>T(p.Leu137Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000116 in 1,210,645 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., 1 hem., cov: 23)

Exomes 𝑓: 0.000010 ( 0 hom. 5 hem. )

Consequence

WDR44
NM_019045.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.146

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:

WDR44 (HGNC:):

WDR44 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=0.031439126).

BS2

High Hemizygotes in GnomAdExome4 at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR44	NM_019045.5 linkuse as main transcript	c.411A>T	p.Leu137Phe	missense_variant	4/20	ENST00000254029.8	NP_061918.3	Q5JSH3-1
WDR44	NM_001184965.2 linkuse as main transcript	c.411A>T	p.Leu137Phe	missense_variant	4/20		NP_001171894.1	Q5JSH3-2
WDR44	NM_001184966.1 linkuse as main transcript	c.336A>T	p.Leu112Phe	missense_variant	3/18		NP_001171895.1	Q5JSH3-4
WDR44	XM_011531353.4 linkuse as main transcript	c.336A>T	p.Leu112Phe	missense_variant	3/19		XP_011529655.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDR44	ENST00000254029.8 linkuse as main transcript	c.411A>T	p.Leu137Phe	missense_variant	4/20	1	NM_019045.5	ENSP00000254029.3		Q5JSH3-1

Frequencies

GnomAD3 genomes

AF:

0.0000266

AC:

AN:

112578

Hom.:

Cov.:

AF XY:

0.0000288

AC XY:

AN XY:

34726

show subpopulations

Gnomad AFR

AF:

0.0000323

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000942

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:

0.00

Gnomad OTH

AF:

0.000656

GnomAD3 exomes

AF:

0.0000164

AC:

AN:

183177

Hom.:

AF XY:

0.0000443

AC XY:

AN XY:

67745

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000365

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:

0.0000245

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000100

AC:

AN:

1098067

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

363421

show subpopulations

Gnomad4 AFR exome

AF:

0.0000379

Gnomad4 AMR exome

AF:

0.0000284

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:

0.00000831

Gnomad4 OTH exome

AF:

0.0000217

GnomAD4 genome

AF:

0.0000266

AC:

AN:

112578

Hom.:

Cov.:

AF XY:

0.0000288

AC XY:

AN XY:

34726

show subpopulations

Gnomad4 AFR

AF:

0.0000323

Gnomad4 AMR

AF:

0.0000942

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000656

Alfa

AF:

0.000102

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 25, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.61

CADD

Benign

5.2

DANN

Benign

0.25

DEOGEN2

Benign

0.14

.;T;.

FATHMM_MKL

Benign

0.046

LIST_S2

Benign

0.53

T;T;T

M_CAP

Benign

0.015

MetaRNN

Benign

0.031

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.34

.;N;N

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.71

N;N;N

REVEL

Benign

0.11

Sift

Benign

0.32

T;T;T

Sift4G

Benign

0.38

T;T;T

Polyphen

0.0

.;B;B

Vest4

0.072

MutPred

0.13

.;Gain of methylation at K138 (P = 0.0495);Gain of methylation at K138 (P = 0.0495);

MVP

0.14

MPC

0.22

ClinPred

0.029

GERP RS

-2.4

Varity_R

0.062

gMVP

0.064

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