9-113321550-T-C

Position:

• chr9-113321550-T-C

Variant summary

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

The NM_001012361.4(WDR31):​c.599A>G​(p.Glu200Gly) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: WDR31 NM_001012361.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.85

Genes affected

WDR31 (HGNC:21421): (WD repeat domain 31) 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. Multiple alternatively spliced transcript variants encoding distinct isoforms have been found for this gene but the biological validity of some variants has not been determined. [provided by RefSeq, Jul 2008]

WDR31 (HGNC:):

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/exons	MANE	Protein	UniProt
WDR31	NM_001012361.4	c.599A>G	p.Glu200Gly	missense_variant	8/11	ENST00000374193.9	NP_001012361.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDR31	ENST00000374193.9	c.599A>G	p.Glu200Gly	missense_variant	8/11	1	NM_001012361.4	ENSP00000363308.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

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

Dec 10, 2024

The c.599A>G (p.E200G) alteration is located in exon 8 (coding exon 6) of the WDR31 gene. This alteration results from a A to G substitution at nucleotide position 599, causing the glutamic acid (E) at amino acid position 200 to be replaced by a glycine (G). 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	Benign	0.26
BayesDel_addAF	Uncertain	0.022	T
BayesDel_noAF	Benign	-0.21
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.00062	.;T;.;.
Eigen	Benign	0.072
Eigen_PC	Benign	0.21
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.81	.;T;T;T
M_CAP	Benign	0.038	D
MetaRNN	Benign	0.30	T;T;T;T
MetaSVM	Benign	-0.62	T
MutationAssessor	Benign	0.76	.;N;.;.
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.30	N;N;.;N
REVEL	Uncertain	0.29
Sift	Benign	0.18	T;T;.;T
Sift4G	Benign	0.35	T;T;T;T
Polyphen		1.0	D;D;D;.
Vest4		0.41
MutPred		0.51		.;Loss of stability (P = 0.05);.;.;
MVP		0.88
MPC		0.30
ClinPred		0.94	D
GERP RS		5.8
Varity_R		0.10
gMVP		0.50

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.21		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.21		Position offset: -39

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

Publications

LitVar

Other links and lift over

dbSNP: rs1833328295; hg19: chr9-116083830;