Variant X-118392642-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PM1BP4_StrongBS2

The NM_019045.5(WDR44):c.197G>T(p.Ser66Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0000471 in 1,188,396 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 26 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000089 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.000051 ( 0 hom. 26 hem. )

Consequence

WDR44
NM_019045.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.39

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 Likely_benign. Variant got -6 ACMG points.

PM1

In a modified_residue Phosphoserine (size 0) in uniprot entity WDR44_HUMAN

BP4

Computational evidence support a benign effect (MetaRNN=0.039993882).

BS2

High Hemizygotes in GnomAdExome4 at 26 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
WDR44	NM_019045.5 linkuse as main transcript	c.197G>T	p.Ser66Ile	missense_variant	4/20	ENST00000254029.8
WDR44	NM_001184965.2 linkuse as main transcript	c.197G>T	p.Ser66Ile	missense_variant	4/20
WDR44	NM_001184966.1 linkuse as main transcript	c.122G>T	p.Ser41Ile	missense_variant	3/18
WDR44	XM_011531353.4 linkuse as main transcript	c.122G>T	p.Ser41Ile	missense_variant	3/19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WDR44	ENST00000254029.8 linkuse as main transcript	c.197G>T	p.Ser66Ile	missense_variant	4/20	1	NM_019045.5	P1	Q5JSH3-1
WDR44	ENST00000371825.7 linkuse as main transcript	c.197G>T	p.Ser66Ile	missense_variant	4/20	1			Q5JSH3-2
WDR44	ENST00000371822.9 linkuse as main transcript	c.122G>T	p.Ser41Ile	missense_variant	3/18	2			Q5JSH3-4
WDR44	ENST00000493448.1 linkuse as main transcript	n.468G>T		non_coding_transcript_exon_variant	3/3	4

Frequencies

GnomAD3 genomes

AF:

0.00000893

AC:

AN:

111976

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34152

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:

0.000375

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000138

AC:

AN:

167089

Hom.:

AF XY:

0.000123

AC XY:

AN XY:

56903

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:

0.00144

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000248

GnomAD4 exome

AF:

0.0000511

AC:

AN:

1076420

Hom.:

Cov.:

AF XY:

0.0000746

AC XY:

AN XY:

348758

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:

0.000841

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.000266

GnomAD4 genome

AF:

0.00000893

AC:

AN:

111976

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34152

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:

0.000375

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.000181

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

Mar 25, 2024

The c.197G>T (p.S66I) alteration is located in exon 4 (coding exon 4) of the WDR44 gene. This alteration results from a G to T substitution at nucleotide position 197, causing the serine (S) at amino acid position 66 to be replaced by an isoleucine (I). 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

0.24

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.20

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.31

.;T;.

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.78

T;D;D

M_CAP

Pathogenic

0.56

MetaRNN

Benign

0.040

T;T;T

MetaSVM

Benign

-0.48

MutationAssessor

Benign

1.5

.;L;L

MutationTaster

Benign

0.99

D;D;D

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-2.0

N;N;N

REVEL

Benign

0.22

Sift

Uncertain

0.0020

D;D;D

Sift4G

Benign

0.11

T;D;D

Polyphen

0.51, 0.65

.;P;P

Vest4

0.47

MutPred

0.26

.;Loss of phosphorylation at S66 (P = 0.0221);Loss of phosphorylation at S66 (P = 0.0221);

MVP

0.45

MPC

0.34

ClinPred

0.19

GERP RS

5.0

Varity_R

0.74

gMVP

0.50

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