chrX-118393184-C-A

Position:

• chrX-118393184-C-A

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4 BS2

The NM_019045.5(WDR44):​c.739C>A​(p.Pro247Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000273 in 1,097,760 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 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: 0.0000027 (0 hom. 2 hem.)
• Consequence: WDR44 NM_019045.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.82

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 Likely_benign. Variant got -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.32734138).
• BS2: High Hemizygotes in GnomAdExome4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WDR44	NM_019045.5	c.739C>A	p.Pro247Thr	missense_variant	4/20	ENST00000254029.8
WDR44	NM_001184965.2	c.739C>A	p.Pro247Thr	missense_variant	4/20
WDR44	NM_001184966.1	c.664C>A	p.Pro222Thr	missense_variant	3/18
WDR44	XM_011531353.4	c.664C>A	p.Pro222Thr	missense_variant	3/19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WDR44	ENST00000254029.8	c.739C>A	p.Pro247Thr	missense_variant	4/20	1	NM_019045.5	P1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 0.00000273 AC: 3 AN: 1097760 Hom.: 0 Cov.: 31 AF XY: 0.00000551 AC XY: 2 AN XY: 363154

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000356

Gnomad4 OTH exome AF: 0.00

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

Apr 01, 2024

The c.739C>A (p.P247T) alteration is located in exon 4 (coding exon 4) of the WDR44 gene. This alteration results from a C to A substitution at nucleotide position 739, causing the proline (P) at amino acid position 247 to be replaced by a threonine (T). 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	Pathogenic	0.72
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.27	.;T;.
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.94	D;D;D
M_CAP	Uncertain	0.16	D
MetaRNN	Benign	0.33	T;T;T
MetaSVM	Benign	-0.80	T
MutationAssessor	Uncertain	2.0	.;M;M
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-1.4	N;N;N
REVEL	Uncertain	0.44
Sift	Uncertain	0.0090	D;D;D
Sift4G	Benign	0.85	T;T;T
Polyphen		1.0	.;D;D
Vest4		0.42
MutPred		0.31		.;Gain of phosphorylation at P247 (P = 2e-04);Gain of phosphorylation at P247 (P = 2e-04);
MVP		0.77
MPC		0.81
ClinPred		0.94	D
GERP RS		5.4
Varity_R		0.55
gMVP		0.51

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-117527147;