X-118392816-C-T

Position:

• chrX-118392816-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_019045.5(WDR44):​c.371C>T​(p.Ala124Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 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: 0.340

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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05902618).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WDR44	NM_019045.5	c.371C>T	p.Ala124Val	missense_variant	4/20	ENST00000254029.8
WDR44	NM_001184965.2	c.371C>T	p.Ala124Val	missense_variant	4/20
WDR44	NM_001184966.1	c.296C>T	p.Ala99Val	missense_variant	3/18
WDR44	XM_011531353.4	c.296C>T	p.Ala99Val	missense_variant	3/19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WDR44	ENST00000254029.8	c.371C>T	p.Ala124Val	missense_variant	4/20	1	NM_019045.5	P1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 31

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

Feb 11, 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	0.070
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	12
DANN	Uncertain	0.99
DEOGEN2	Benign	0.12	.;T;.
FATHMM_MKL	Benign	0.42	N
LIST_S2	Benign	0.66	T;T;T
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.059	T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.8	.;L;L
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.38	N;N;N
REVEL	Benign	0.078
Sift	Benign	0.059	T;T;T
Sift4G	Benign	0.27	T;T;T
Polyphen		0.56, 0.69	.;P;P
Vest4		0.12
MutPred		0.14		.;Loss of helix (P = 0.0558);Loss of helix (P = 0.0558);
MVP		0.28
MPC		0.20
ClinPred		0.12	T
GERP RS		1.6
Varity_R		0.052
gMVP		0.089

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.20		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.20		Position offset: -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-117526779;