Genetic Variant NM_001369450.1:c.710C>A (chr11-62834436-G-T) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_001369450.1(WDR74):c.710C>A(p.Pro237Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000351 in 1,139,822 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P237L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 26)

Exomes 𝑓: 0.0000035 ( 0 hom. )

Consequence

WDR74
NM_001369450.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.00

Publications

0 publications found

Variant links:

Genes affected

WDR74 (HGNC:25529): (WD repeat domain 74) Involved in rRNA processing and ribosomal large subunit biogenesis. Located in nucleoplasm. Colocalizes with nuclear exosome (RNase complex) and nucleolus. [provided by Alliance of Genome Resources, Apr 2022]

WDR74 links:

STX5-DT (HGNC:55488): (STX5 divergent transcript)

STX5-DT links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.746

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001369450.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
WDR74	NM_001369450.1	MANE Select	c.710C>A	p.Pro237Gln	missense	Exon 7 of 11	NP_001356379.1	Q6RFH5-1
WDR74	NM_001369447.1		c.752C>A	p.Pro251Gln	missense	Exon 7 of 11	NP_001356376.1
WDR74	NM_001369451.1		c.710C>A	p.Pro237Gln	missense	Exon 8 of 12	NP_001356380.1	Q6RFH5-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
WDR74	ENST00000278856.9	TSL:1 MANE Select	c.710C>A	p.Pro237Gln	missense	Exon 7 of 11	ENSP00000278856.4	Q6RFH5-1
WDR74	ENST00000311713.11	TSL:1	c.710C>A	p.Pro237Gln	missense	Exon 7 of 10	ENSP00000308931.7	Q6RFH5-2
WDR74	ENST00000892916.1		c.752C>A	p.Pro251Gln	missense	Exon 8 of 12	ENSP00000562975.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000404

AC:

AN:

247290

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.00000351

AC:

AN:

1139822

Hom.:

Cov.:

AF XY:

0.00000352

AC XY:

AN XY:

567902

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

24878

American (AMR)

AF:

0.00

AC:

AN:

37534

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16748

East Asian (EAS)

AF:

0.00

AC:

AN:

17424

South Asian (SAS)

AF:

0.0000365

AC:

AN:

82168

European-Finnish (FIN)

AF:

0.00

AC:

AN:

34240

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4294

European-Non Finnish (NFE)

AF:

0.00000114

AC:

AN:

880794

Other (OTH)

AF:

0.00

AC:

AN:

41742

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

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.:

ExAC

AF:

0.0000165

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

Benign

0.12

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.32

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.19

Eigen

Uncertain

0.49

Eigen_PC

Uncertain

0.48

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.83

M_CAP

Benign

0.016

MetaRNN

Pathogenic

0.75

MetaSVM

Benign

-0.90

MutationAssessor

Uncertain

2.2

PhyloP100

5.0

PrimateAI

Uncertain

0.53

PROVEAN

Uncertain

-3.6

REVEL

Benign

0.21

Sift

Uncertain

0.013

Sift4G

Uncertain

0.031

Polyphen

0.99

Vest4

0.70

MutPred

0.49

Loss of glycosylation at T234 (P = 0.0424)

MVP

0.65

MPC

0.42

ClinPred

0.91

GERP RS

4.3

Varity_R

0.19

gMVP

0.54

Mutation Taster

=76/24

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over