Variant X-118395319-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_019045.5(WDR44):c.1028A>G(p.Asn343Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000639 in 1,095,277 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes 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: 0.0000064 ( 0 hom. 1 hem. )

Consequence

WDR44
NM_019045.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.11

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.13802966).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR44	NM_019045.5 linkuse as main transcript	c.1028A>G	p.Asn343Ser	missense_variant	6/20	ENST00000254029.8	NP_061918.3	Q5JSH3-1
WDR44	NM_001184965.2 linkuse as main transcript	c.1028A>G	p.Asn343Ser	missense_variant	6/20		NP_001171894.1	Q5JSH3-2
WDR44	NM_001184966.1 linkuse as main transcript	c.953A>G	p.Asn318Ser	missense_variant	5/18		NP_001171895.1	Q5JSH3-4
WDR44	XM_011531353.4 linkuse as main transcript	c.953A>G	p.Asn318Ser	missense_variant	5/19		XP_011529655.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
WDR44	ENST00000254029.8 linkuse as main transcript	c.1028A>G	p.Asn343Ser	missense_variant	6/20	1	NM_019045.5	ENSP00000254029.3	Q5JSH3-1
WDR44	ENST00000371825.7 linkuse as main transcript	c.1028A>G	p.Asn343Ser	missense_variant	6/20	1		ENSP00000360890.3	Q5JSH3-2
WDR44	ENST00000371848.3 linkuse as main transcript	c.725A>G	p.Asn242Ser	missense_variant	3/18	1		ENSP00000360914.3	H7BY83
WDR44	ENST00000371822.9 linkuse as main transcript	c.953A>G	p.Asn318Ser	missense_variant	5/18	2		ENSP00000360887.5	Q5JSH3-4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000165

AC:

AN:

181375

Hom.:

AF XY:

0.00

AC XY:

AN XY:

65907

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000220

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:

0.00000639

AC:

AN:

1095277

Hom.:

Cov.:

AF XY:

0.00000277

AC XY:

AN XY:

360773

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000232

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:

0.00000756

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

Dec 15, 2023

The c.1028A>G (p.N343S) alteration is located in exon 6 (coding exon 6) of the WDR44 gene. This alteration results from a A to G substitution at nucleotide position 1028, causing the asparagine (N) at amino acid position 343 to be replaced by a serine (S). 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

0.11

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.18

.;T;.

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.90

D;D;D

M_CAP

Uncertain

0.25

MetaRNN

Benign

0.14

T;T;T

MetaSVM

Benign

-0.76

MutationAssessor

Uncertain

2.0

.;M;M

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-0.90

N;N;N

REVEL

Benign

0.089

Sift

Benign

0.19

T;T;T

Sift4G

Benign

0.21

T;T;T

Polyphen

0.0, 0.0010

.;B;B

Vest4

0.38

MutPred

0.23

.;Gain of phosphorylation at N343 (P = 0.0046);Gain of phosphorylation at N343 (P = 0.0046);

MVP

0.50

MPC

0.16

ClinPred

0.23

GERP RS

5.5

Varity_R

0.29

gMVP

0.43

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