rs782080281

Variant names:

• chrX-48600377-C-G
• NM_001347217.2:c.582C>G

Your query was ambiguous. Multiple possible variants found:

• chrX-48600377-C-G
• chrX-48600377-C-T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_001347217.2(WDR13):​c.582C>G​(p.Asp194Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000913 in 1,095,592 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 25)
  • Exomes 𝑓: 9.1e-7 (0 hom. 0 hem.)
• Consequence: WDR13 NM_001347217.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.27

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 Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.973

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR13	NM_001347217.2	c.582C>G	p.Asp194Glu	missense_variant	Exon 6 of 10	ENST00000376729.10	NP_001334146.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDR13	ENST00000376729.10	c.582C>G	p.Asp194Glu	missense_variant	Exon 6 of 10	5	NM_001347217.2	ENSP00000365919.5

Frequencies

GnomAD3 genomes Cov.: 25

GnomAD4 exome AF: 9.13e-7 AC: 1 AN: 1095592 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 361876

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: 0.0000260

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 25

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Pathogenic	0.32	D
BayesDel_noAF	Pathogenic	0.22
CADD	Benign	16
DANN	Uncertain	1.0
FATHMM_MKL	Benign	0.23	N
M_CAP	Uncertain	0.18	D
MetaRNN	Pathogenic	0.97	D;D
MetaSVM	Uncertain	-0.046	T
PrimateAI	Uncertain	0.78	T
PROVEAN	Uncertain	-3.8	D;D
REVEL	Uncertain	0.62
Sift	Uncertain	0.0030	D;D
Sift4G	Pathogenic	0.0	D;D
Vest4		0.91
MutPred		0.92		Loss of stability (P = 0.3538);Loss of stability (P = 0.3538);
MVP		0.93
MPC		2.0
ClinPred		0.98	D
GERP RS		-3.5
gMVP		0.96

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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-48458765;