chrX-48600543-C-A

Variant names:

• chrX-48600543-C-A
• NM_001347217.2:c.748C>A

Variant summary

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

The NM_001347217.2(WDR13):​c.748C>A​(p.Arg250Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000364 in 1,097,830 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. 11/18 in silico tools predict a benign 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: 0.0000036 (0 hom. 1 hem.)
• Consequence: WDR13 NM_001347217.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.18

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.748C>A	p.Arg250Ser	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.748C>A	p.Arg250Ser	missense_variant	Exon 6 of 10	5	NM_001347217.2	ENSP00000365919.5

Frequencies

GnomAD3 genomes Cov.: 25

GnomAD4 exome AF: 0.00000364 AC: 4 AN: 1097830 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 1 AN XY: 363204

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: 0.00

Gnomad4 NFE exome AF: 0.00000475

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	Benign	0.25
BayesDel_addAF	Uncertain	0.034	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	22
DANN	Benign	0.96
FATHMM_MKL	Uncertain	0.94	D
M_CAP	Benign	0.039	D
MetaRNN	Uncertain	0.50	T;T
MetaSVM	Benign	-0.98	T
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	0.31	N;N
REVEL	Benign	0.27
Sift	Benign	0.86	T;T
Sift4G	Benign	0.82	T;T
Vest4		0.60
MutPred		0.55		Gain of phosphorylation at R250 (P = 0.0578);Gain of phosphorylation at R250 (P = 0.0578);
MVP		0.65
MPC		1.1
ClinPred		0.98	D
GERP RS		4.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
gMVP		0.62

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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-48458931;