X-49074847-C-A

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2 BP4 BP6_Moderate

The NM_001029896.2(WDR45):c.1039G>T(p.Ala347Ser) 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. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 24)
• Consequence: WDR45 NM_001029896.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 7.15

Genes affected

WDR45 (HGNC:28912): (WD repeat domain 45) This gene encodes a member of the WD repeat protein family. WD repeats are minimally conserved regions of approximately 40 amino acids typically bracketed by gly-his and trp-asp (GH-WD), which may facilitate formation of heterotrimeric or multiprotein complexes. Members of this family are involved in a variety of cellular processes, including cell cycle progression, signal transduction, apoptosis, and gene regulation. This gene has a pseudogene at chromosome 4q31.3. Multiple alternatively spliced transcript variants encoding distinct isoforms have been found for this gene, but the biological validity and full-length nature of some variants have not been determined. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_benign. Variant got -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.39903536).
• BP6: Variant X-49074847-C-A is Benign according to our data. Variant chrX-49074847-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 1635694.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WDR45	NM_001029896.2	c.1039G>T	p.Ala347Ser	missense_variant	11/11	ENST00000376372.9
WDR45	NM_007075.4	c.1042G>T	p.Ala348Ser	missense_variant	12/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WDR45	ENST00000376372.9	c.1039G>T	p.Ala347Ser	missense_variant	11/11	1	NM_001029896.2	P4

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 24

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Neurodegeneration with brain iron accumulation 5 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Feb 09, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Benign	-0.0090	T
BayesDel_noAF	Benign	-0.25
Cadd	Benign	20
Dann	Benign	0.90
DEOGEN2	Benign	0.028	T;T;T;.;T;.;.;.;.;T
FATHMM_MKL	Uncertain	0.95	D
M_CAP	Pathogenic	0.60	D
MetaRNN	Benign	0.40	T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	-0.16	N;N;.;.;.;.;.;.;.;.
MutationTaster	Benign	1.0	D;D;D;D;D;D;D;D
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-0.27	N;.;.;.;.;N;N;N;N;.
REVEL	Uncertain	0.29
Sift	Benign	0.77	T;.;.;.;.;T;T;T;T;.
Sift4G	Benign	0.95	T;T;T;T;T;T;T;T;T;T
Polyphen		0.012	B;B;.;.;.;B;B;B;B;.
Vest4		0.43
MutPred		0.62		Gain of sheet (P = 0.1451);Gain of sheet (P = 0.1451);.;.;.;.;.;.;.;.;
MVP		0.74
MPC		0.59
ClinPred		0.81	D
GERP RS		5.0
Varity_R		0.33
gMVP		0.59

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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-48932506;