X-48601844-G-A

Variant names:

• chrX-48601844-G-A
• rs201415075
• NM_001347217.2:c.892G>A

Variant summary

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

The NM_001347217.2(WDR13):​c.892G>A​(p.Gly298Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000184 in 1,089,833 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 0.0000018 (0 hom. 1 hem.)
• Consequence: WDR13 NM_001347217.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.64

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR13	NM_001347217.2	c.892G>A	p.Gly298Arg	missense_variant	Exon 7 of 10	ENST00000376729.10	NP_001334146.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDR13	ENST00000376729.10	c.892G>A	p.Gly298Arg	missense_variant	Exon 7 of 10	5	NM_001347217.2	ENSP00000365919.5
WDR13	ENST00000218056.9	c.892G>A	p.Gly298Arg	missense_variant	Exon 6 of 9	1		ENSP00000218056.5
WDR13	ENST00000479279.5	n.1759G>A		non_coding_transcript_exon_variant	Exon 5 of 8	1
WDR13	ENST00000482760.3	c.136G>A	p.Gly46Arg	missense_variant	Exon 2 of 5	3		ENSP00000483191.1

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD3 exomes AF: 0.00000581 AC: 1 AN: 172041 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 57995

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000598

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000184 AC: 2 AN: 1089833 Hom.: 0 Cov.: 31 AF XY: 0.00000280 AC XY: 1 AN XY: 356857

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: 0.0000378

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 24

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.96
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.33
CADD	Pathogenic	28
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.11	.;.;T
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.96	.;.;D
M_CAP	Uncertain	0.22	D
MetaRNN	Uncertain	0.60	D;D;D
MetaSVM	Benign	-0.54	T
PrimateAI	Pathogenic	0.86	D
PROVEAN	Pathogenic	-4.5	D;D;.
REVEL	Uncertain	0.47
Sift	Uncertain	0.0030	D;D;.
Sift4G	Uncertain	0.0030	D;D;D
Vest4		0.42
MutPred		0.26		Gain of MoRF binding (P = 0.0432);Gain of MoRF binding (P = 0.0432);.;
MVP		0.83
MPC		2.3
ClinPred		0.81	D
GERP RS		5.4
gMVP		0.82

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs201415075; hg19: chrX-48460232;