X-118397082-T-G

Position:

• chrX-118397082-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_019045.5(WDR44):​c.1166T>G​(p.Met389Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 22)
• Consequence: WDR44 NM_019045.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.97

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.897

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR44	NM_019045.5	c.1166T>G	p.Met389Arg	missense_variant	7/20	ENST00000254029.8	NP_061918.3
WDR44	NM_001184965.2	c.1166T>G	p.Met389Arg	missense_variant	7/20		NP_001171894.1
WDR44	NM_001184966.1	c.1091T>G	p.Met364Arg	missense_variant	6/18		NP_001171895.1
WDR44	XM_011531353.4	c.1091T>G	p.Met364Arg	missense_variant	6/19		XP_011529655.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDR44	ENST00000254029.8	c.1166T>G	p.Met389Arg	missense_variant	7/20	1	NM_019045.5	ENSP00000254029.3
WDR44	ENST00000371825.7	c.1166T>G	p.Met389Arg	missense_variant	7/20	1		ENSP00000360890.3
WDR44	ENST00000371848.3	c.863T>G	p.Met288Arg	missense_variant	4/18	1		ENSP00000360914.3
WDR44	ENST00000371822.9	c.1091T>G	p.Met364Arg	missense_variant	6/18	2		ENSP00000360887.5

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 22

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

Oct 03, 2022

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on 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 (Richards et al., 2015) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.50	D
BayesDel_noAF	Pathogenic	0.48
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.67	.;D;.
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D;D;D
M_CAP	Pathogenic	0.75	D
MetaRNN	Pathogenic	0.90	D;D;D
MetaSVM	Uncertain	0.26	D
MutationAssessor	Uncertain	2.0	.;M;M
PrimateAI	Pathogenic	0.89	D
PROVEAN	Uncertain	-4.2	D;D;D
REVEL	Pathogenic	0.82
Sift	Uncertain	0.0010	D;D;D
Sift4G	Uncertain	0.0040	D;D;D
Polyphen		0.99, 1.0	.;D;D
Vest4		0.87
MutPred		0.48		.;Gain of MoRF binding (P = 0.0327);Gain of MoRF binding (P = 0.0327);
MVP		0.93
MPC		2.7
ClinPred		1.0	D
GERP RS		5.9
Varity_R		0.96
gMVP		0.94

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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-117531045;