X-48601956-T-G

Position:

• chrX-48601956-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP2 PP3

The NM_001347217.2(WDR13):​c.1004T>G​(p.Met335Arg) variant causes a missense change. 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: 24)
• Consequence: WDR13 NM_001347217.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.22

Genes affected

WDR13 (HGNC:14352): (WD repeat domain 13) 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. A similar protein in mouse is thought to be a negative regulator of the pancreatic beta cell proliferation. Mice lacking this gene exhibit increased pancreatic islet mass and higher serum insulin levels, and are mildly obese. [provided by RefSeq, Nov 2016]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant in gene, where missense usually causes diseases (based on misZ statistic), WDR13. . Gene score misZ 3.2948 (greater than the threshold 3.09). GenCC has associacion of gene with intellectual disability.
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.761

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR13	NM_001347217.2	c.1004T>G	p.Met335Arg	missense_variant	7/10	ENST00000376729.10	NP_001334146.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDR13	ENST00000376729.10	c.1004T>G	p.Met335Arg	missense_variant	7/10	5	NM_001347217.2	ENSP00000365919	P1
WDR13	ENST00000218056.9	c.1004T>G	p.Met335Arg	missense_variant	6/9	1		ENSP00000218056	P1
WDR13	ENST00000479279.5	n.1871T>G		non_coding_transcript_exon_variant	5/8	1
WDR13	ENST00000482760.3	c.248T>G	p.Met83Arg	missense_variant	2/5	3		ENSP00000483191

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 24

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

Jan 23, 2024

The c.1004T>G (p.M335R) alteration is located in exon 6 (coding exon 6) of the WDR13 gene. This alteration results from a T to G substitution at nucleotide position 1004, causing the methionine (M) at amino acid position 335 to be replaced by an arginine (R). 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	0.70
BayesDel_addAF	Pathogenic	0.32	D
BayesDel_noAF	Pathogenic	0.22
CADD	Benign	22
DANN	Benign	0.69
DEOGEN2	Benign	0.031	.;.;T
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.92	.;.;D
M_CAP	Uncertain	0.20	D
MetaRNN	Pathogenic	0.76	D;D;D
MetaSVM	Benign	-0.88	T
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-1.7	N;N;.
REVEL	Uncertain	0.39
Sift	Benign	0.64	T;T;.
Sift4G	Benign	0.11	T;T;D
Vest4		0.64
MutPred		0.66		Gain of MoRF binding (P = 0.0179);Gain of MoRF binding (P = 0.0179);.;
MVP		0.97
MPC		1.6
ClinPred		0.83	D
GERP RS		5.4
gMVP		0.98

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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-48460344;