Genetic Variant WDR31:p.Val285Phe (chr9-113318565-C-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001012361.4(WDR31):c.853G>T(p.Val285Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,886 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. V285I) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

WDR31
NM_001012361.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.628

Publications

0 publications found

Variant links:

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 links:

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ACMG classification

Classification was made for transcript

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
WDR31	NM_001012361.4	MANE Select	c.853G>T	p.Val285Phe	missense	Exon 10 of 11	NP_001012361.1	Q8NA23-1
WDR31	NM_145241.5		c.850G>T	p.Val284Phe	missense	Exon 10 of 11	NP_660284.1	Q8NA23-2
WDR31	NM_001006615.3		c.478G>T	p.Val160Phe	missense	Exon 9 of 10	NP_001006616.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
WDR31	ENST00000374193.9	TSL:1 MANE Select	c.853G>T	p.Val285Phe	missense	Exon 10 of 11	ENSP00000363308.3	Q8NA23-1
WDR31	ENST00000461942.5	TSL:1	n.1042G>T		non_coding_transcript_exon	Exon 10 of 11
WDR31	ENST00000944273.1		c.865G>T	p.Val289Phe	missense	Exon 9 of 10	ENSP00000614332.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461886

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727242

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1112010

Other (OTH)

AF:

0.0000166

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Uncertain

0.081

BayesDel_noAF

Benign

-0.12

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.012

Eigen

Uncertain

0.32

Eigen_PC

Uncertain

0.32

FATHMM_MKL

Benign

0.71

LIST_S2

Benign

0.75

M_CAP

Benign

0.023

MetaRNN

Uncertain

0.74

MetaSVM

Benign

-0.65

MutationAssessor

Uncertain

2.2

PhyloP100

0.63

PrimateAI

Benign

0.42

PROVEAN

Benign

-2.3

REVEL

Uncertain

0.29

Sift

Uncertain

0.018

Sift4G

Uncertain

0.018

Polyphen

0.95

Vest4

0.81

MutPred

0.54

Loss of helix (P = 0.3949)

MVP

0.81

MPC

0.16

ClinPred

0.96

GERP RS

4.3

Varity_R

0.30

gMVP

0.57

Mutation Taster

=84/16

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over