X-118409555-G-T

Position:

• chrX-118409555-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_019045.5(WDR44):​c.1600G>T​(p.Val534Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. 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: 3.80

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29650557).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR44	NM_019045.5	c.1600G>T	p.Val534Leu	missense_variant	11/20	ENST00000254029.8	NP_061918.3
WDR44	NM_001184965.2	c.1600G>T	p.Val534Leu	missense_variant	11/20		NP_001171894.1
WDR44	NM_001184966.1	c.1525G>T	p.Val509Leu	missense_variant	10/18		NP_001171895.1
WDR44	XM_011531353.4	c.1525G>T	p.Val509Leu	missense_variant	10/19		XP_011529655.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDR44	ENST00000254029.8	c.1600G>T	p.Val534Leu	missense_variant	11/20	1	NM_019045.5	ENSP00000254029.3
WDR44	ENST00000371825.7	c.1600G>T	p.Val534Leu	missense_variant	11/20	1		ENSP00000360890.3
WDR44	ENST00000371848.3	c.1297G>T	p.Val433Leu	missense_variant	8/18	1		ENSP00000360914.3
WDR44	ENST00000371822.9	c.1525G>T	p.Val509Leu	missense_variant	10/18	2		ENSP00000360887.5

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 18, 2023

The c.1600G>T (p.V534L) alteration is located in exon 11 (coding exon 11) of the WDR44 gene. This alteration results from a G to T substitution at nucleotide position 1600, causing the valine (V) at amino acid position 534 to be replaced by a leucine (L). 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	0.16
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.23	.;T;.
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.94	D;D;D
M_CAP	Benign	0.050	D
MetaRNN	Benign	0.30	T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.14	.;N;N
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-1.7	N;N;N
REVEL	Benign	0.21
Sift	Benign	0.046	D;T;T
Sift4G	Uncertain	0.028	D;D;D
Polyphen		0.038, 0.066	.;B;B
Vest4		0.55
MutPred		0.56		.;Loss of MoRF binding (P = 0.1001);Loss of MoRF binding (P = 0.1001);
MVP		0.36
MPC		1.1
ClinPred		0.35	T
GERP RS		4.2
Varity_R		0.12
gMVP		0.68

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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-117543518;