9-113318615-C-A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Publications: 3 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001012361.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR31	NM_001012361.4	MANE Select	c.803G>T	p.Arg268Leu	missense	Exon 10 of 11	NP_001012361.1	Q8NA23-1
	WDR31	NM_145241.5		c.800G>T	p.Arg267Leu	missense	Exon 10 of 11	NP_660284.1	Q8NA23-2
	WDR31	NM_001006615.3		c.428G>T	p.Arg143Leu	missense	Exon 9 of 10	NP_001006616.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR31	ENST00000374193.9	TSL:1 MANE Select	c.803G>T	p.Arg268Leu	missense	Exon 10 of 11	ENSP00000363308.3	Q8NA23-1
	WDR31	ENST00000461942.5	TSL:1	n.992G>T		non_coding_transcript_exon	Exon 10 of 11
	WDR31	ENST00000944273.1		c.815G>T	p.Arg272Leu	missense	Exon 9 of 10	ENSP00000614332.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.017	T
MetaRNN	Uncertain	0.72	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		3.0
PrimateAI	Uncertain	0.50	T
PROVEAN	Uncertain	-3.3	D
REVEL	Benign	0.14
Sift	Benign	0.042	D
Sift4G	Benign	0.14	T
Polyphen		0.55	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
Mutation Taster		=80/20	polymorphism

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

Other links and lift over

dbSNP: rs373131738; hg19: chr9-116080895;