X-118406911-A-T

Position:

• chrX-118406911-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_019045.5(WDR44):​c.1418A>T​(p.Asp473Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: WDR44 NM_019045.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.27

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR44	NM_019045.5	c.1418A>T	p.Asp473Val	missense_variant	10/20	ENST00000254029.8	NP_061918.3
WDR44	NM_001184965.2	c.1418A>T	p.Asp473Val	missense_variant	10/20		NP_001171894.1
WDR44	NM_001184966.1	c.1343A>T	p.Asp448Val	missense_variant	9/18		NP_001171895.1
WDR44	XM_011531353.4	c.1343A>T	p.Asp448Val	missense_variant	9/19		XP_011529655.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDR44	ENST00000254029.8	c.1418A>T	p.Asp473Val	missense_variant	10/20	1	NM_019045.5	ENSP00000254029.3
WDR44	ENST00000371825.7	c.1418A>T	p.Asp473Val	missense_variant	10/20	1		ENSP00000360890.3
WDR44	ENST00000371848.3	c.1115A>T	p.Asp372Val	missense_variant	7/18	1		ENSP00000360914.3
WDR44	ENST00000371822.9	c.1343A>T	p.Asp448Val	missense_variant	9/18	2		ENSP00000360887.5

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

GeneDx

Apr 19, 2024

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis indicates that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; Variants in candidate genes are classified as variants of uncertain significance in accordance with ACMG guidelines (PMID: 25741868) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.30	D
BayesDel_noAF	Pathogenic	0.19
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.23	.;T;.
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D;D;D
M_CAP	Pathogenic	0.71	D
MetaRNN	Uncertain	0.65	D;D;D
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	0.66	.;N;N
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-0.85	N;N;N
REVEL	Uncertain	0.40
Sift	Benign	0.18	T;T;T
Sift4G	Benign	0.35	T;T;T
Polyphen		0.23, 1.0	.;B;D
Vest4		0.76
MutPred		0.24		.;Gain of catalytic residue at D473 (P = 0.0107);Gain of catalytic residue at D473 (P = 0.0107);
MVP		0.87
MPC		2.2
ClinPred		0.80	D
GERP RS		5.8
Varity_R		0.55
gMVP		0.75

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-117540874;