Genetic Variant NM_001369450.1:c.589A>G (chr11-62835460-T-C) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_001369450.1(WDR74):c.589A>G(p.Lys197Glu) variant causes a missense change. The variant allele was found at a frequency of 0.0000359 in 1,613,966 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00021 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

WDR74
NM_001369450.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.61

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: Likely_benign. The variant received -1 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.3926553).

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.589A>G	p.Lys197Glu	missense	Exon 6 of 11	NP_001356379.1	Q6RFH5-1
WDR74	NM_001369447.1		c.631A>G	p.Lys211Glu	missense	Exon 6 of 11	NP_001356376.1
WDR74	NM_001369451.1		c.589A>G	p.Lys197Glu	missense	Exon 7 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.589A>G	p.Lys197Glu	missense	Exon 6 of 11	ENSP00000278856.4	Q6RFH5-1
WDR74	ENST00000311713.11	TSL:1	c.589A>G	p.Lys197Glu	missense	Exon 6 of 10	ENSP00000308931.7	Q6RFH5-2
WDR74	ENST00000892916.1		c.631A>G	p.Lys211Glu	missense	Exon 7 of 12	ENSP00000562975.1

Frequencies

GnomAD3 genomes

AF:

0.000210

AC:

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000773

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000321

AC:

AN:

249222

AF XY:

0.0000370

show subpopulations

Gnomad AFR exome

AF:

0.000452

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:

0.00000885

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000178

AC:

AN:

1461684

Hom.:

Cov.:

AF XY:

0.0000165

AC XY:

AN XY:

727128

show subpopulations

African (AFR)

AF:

0.000717

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26126

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53402

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111854

Other (OTH)

AF:

0.0000166

AC:

AN:

60374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.446

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

AF:

0.000210

AC:

AN:

152282

Hom.:

Cov.:

AF XY:

0.000215

AC XY:

AN XY:

74460

show subpopulations

African (AFR)

AF:

0.000770

AC:

AN:

41536

American (AMR)

AF:

0.00

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68020

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.0000604

Hom.:

Bravo

AF:

0.000212

ESP6500AA

AF:

0.000995

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000331

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

Uncertain

0.40

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.20

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.019

Eigen

Uncertain

0.59

Eigen_PC

Uncertain

0.61

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.90

M_CAP

Benign

0.014

MetaRNN

Benign

0.39

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.9

PhyloP100

4.6

PrimateAI

Uncertain

0.75

PROVEAN

Benign

-1.4

REVEL

Benign

0.15

Sift

Uncertain

0.0090

Sift4G

Uncertain

0.012

Polyphen

0.98

Vest4

0.63

MVP

0.63

MPC

1.0

ClinPred

0.23

GERP RS

5.5

Varity_R

0.36

gMVP

0.83

Mutation Taster

=69/31

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over