Genetic Variant WDR31:p.Cys248Tyr (chr9-113320394-C-T) – 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.743G>A(p.Cys248Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,860 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

WDR31
NM_001012361.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.11

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.743G>A	p.Cys248Tyr	missense	Exon 9 of 11	NP_001012361.1	Q8NA23-1
WDR31	NM_145241.5		c.740G>A	p.Cys247Tyr	missense	Exon 9 of 11	NP_660284.1	Q8NA23-2
WDR31	NM_001006615.3		c.368G>A	p.Cys123Tyr	missense	Exon 8 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.743G>A	p.Cys248Tyr	missense	Exon 9 of 11	ENSP00000363308.3	Q8NA23-1
WDR31	ENST00000461942.5	TSL:1	n.932G>A		non_coding_transcript_exon	Exon 9 of 11
WDR31	ENST00000944273.1		c.743G>A	p.Cys248Tyr	missense	Exon 8 of 10	ENSP00000614332.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000119

AC:

AN:

251298

AF XY:

0.0000147

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000868

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461860

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727228

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.0000447

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.00

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111990

Other (OTH)

AF:

0.00

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.00000824

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.80

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.20

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.074

Eigen

Pathogenic

0.74

Eigen_PC

Pathogenic

0.73

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.90

M_CAP

Benign

0.029

MetaRNN

Uncertain

0.54

MetaSVM

Benign

-1.2

MutationAssessor

Uncertain

2.6

PhyloP100

4.1

PrimateAI

Uncertain

0.56

PROVEAN

Pathogenic

-4.6

REVEL

Benign

0.24

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.033

Polyphen

1.0

Vest4

0.49

MutPred

0.46

Loss of ubiquitination at K244 (P = 0.0787)

MVP

0.48

MPC

0.65

ClinPred

0.97

GERP RS

5.8

Varity_R

0.75

gMVP

0.67

Mutation Taster

=70/30

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over