X-118432815-A-G

Position:

• chrX-118432815-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_019045.5(WDR44):​c.1772A>G​(p.Lys591Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000182 in 1,097,796 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples 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: 0.0000018 (0 hom. 0 hem.)
• Consequence: WDR44 NM_019045.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.05

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19654068).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WDR44	NM_019045.5	c.1772A>G	p.Lys591Arg	missense_variant	13/20	ENST00000254029.8
WDR44	NM_001184965.2	c.1772A>G	p.Lys591Arg	missense_variant	13/20
WDR44	NM_001184966.1	c.1697A>G	p.Lys566Arg	missense_variant	12/18
WDR44	XM_011531353.4	c.1697A>G	p.Lys566Arg	missense_variant	12/19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WDR44	ENST00000254029.8	c.1772A>G	p.Lys591Arg	missense_variant	13/20	1	NM_019045.5	P1
WDR44	ENST00000371825.7	c.1772A>G	p.Lys591Arg	missense_variant	13/20	1
WDR44	ENST00000371848.3	c.1472A>G	p.Lys491Arg	missense_variant	10/18	1
WDR44	ENST00000371822.9	c.1697A>G	p.Lys566Arg	missense_variant	12/18	2

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 0.00000182 AC: 2 AN: 1097796 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 363166

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: 0.00000238

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 provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

GeneDx

Jan 05, 2022

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports 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 (Richards et al., 2015) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	.;T;.
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Uncertain	0.87	D;D;D
M_CAP	Uncertain	0.10	D
MetaRNN	Benign	0.20	T;T;T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	-0.29	.;N;N
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-0.39	N;N;N
REVEL	Benign	0.083
Sift	Benign	0.25	T;T;T
Sift4G	Benign	0.61	T;T;T
Polyphen		0.0010, 0.0050	.;B;B
Vest4		0.13
MutPred		0.32		.;Loss of ubiquitination at K591 (P = 0.0047);Loss of ubiquitination at K591 (P = 0.0047);
MVP		0.45
MPC		0.90
ClinPred		0.85	D
GERP RS		5.4
Varity_R		0.32
gMVP		0.15

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-117566778;