9-113318615-C-A

Variant names:

• chr9-113318615-C-A
• rs373131738
• NM_001012361.4:c.803G>T

Variant summary

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

The NM_001012361.4(WDR31):​c.803G>T​(p.Arg268Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R268Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: WDR31 NM_001012361.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.02

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]

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
WDR31	NM_001012361.4	c.803G>T	p.Arg268Leu	missense_variant	Exon 10 of 11	ENST00000374193.9	NP_001012361.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDR31	ENST00000374193.9	c.803G>T	p.Arg268Leu	missense_variant	Exon 10 of 11	1	NM_001012361.4	ENSP00000363308.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.063	.;T;.
Eigen	Benign	0.030
Eigen_PC	Benign	0.057
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Uncertain	0.90	.;D;D
M_CAP	Benign	0.017	T
MetaRNN	Uncertain	0.72	D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.7	.;M;.
PrimateAI	Uncertain	0.50	T
PROVEAN	Uncertain	-3.3	D;D;.
REVEL	Benign	0.14
Sift	Benign	0.042	D;D;.
Sift4G	Benign	0.14	T;T;T
Polyphen		0.55	P;P;P
Vest4		0.63
MutPred		0.61		.;Loss of catalytic residue at R268 (P = 0.1926);.;
MVP		0.38
MPC		0.55
ClinPred		0.99	D
GERP RS		5.0
Varity_R		0.42
gMVP		0.44

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: rs373131738; hg19: chr9-116080895;