Genetic Variant NM_145294.5:c.3001C>A (chr16-659001-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_145294.5(WDR90):c.3001C>A(p.Pro1001Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.431 in 1,612,822 control chromosomes in the GnomAD database, including 169,311 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.55 ( 26232 hom., cov: 33)

Exomes 𝑓: 0.42 ( 143079 hom. )

Consequence

WDR90
NM_145294.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.604

Publications

38 publications found

Variant links:

Genes affected

WDR90 (HGNC:26960): (WD repeat domain 90) Involved in cilium assembly. Located in centriole. [provided by Alliance of Genome Resources, Apr 2022]

WDR90 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.2617623E-6).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.954 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR90	NM_145294.5 link	c.3001C>A	p.Pro1001Thr	missense_variant	Exon 24 of 41	ENST00000293879.9	NP_660337.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDR90	ENST00000293879.9 link	c.3001C>A	p.Pro1001Thr	missense_variant	Exon 24 of 41	5	NM_145294.5	ENSP00000293879.4

Frequencies

GnomAD3 genomes

AF:

0.547

AC:

83028

AN:

151918

Hom.:

26176

Cov.:

show subpopulations

Gnomad AFR

AF:

0.819

Gnomad AMI

AF:

0.269

Gnomad AMR

AF:

0.583

Gnomad ASJ

AF:

0.349

Gnomad EAS

AF:

0.977

Gnomad SAS

AF:

0.551

Gnomad FIN

AF:

0.486

Gnomad MID

AF:

0.398

Gnomad NFE

AF:

0.365

Gnomad OTH

AF:

0.477

GnomAD2 exomes

AF:

0.523

AC:

130041

AN:

248430

AF XY:

0.506

show subpopulations

Gnomad AFR exome

AF:

0.839

Gnomad AMR exome

AF:

0.707

Gnomad ASJ exome

AF:

0.332

Gnomad EAS exome

AF:

0.984

Gnomad FIN exome

AF:

0.488

Gnomad NFE exome

AF:

0.369

Gnomad OTH exome

AF:

0.445

GnomAD4 exome

AF:

0.419

AC:

611854

AN:

1460786

Hom.:

143079

Cov.:

AF XY:

0.420

AC XY:

305391

AN XY:

726680

show subpopulations

African (AFR)

AF:

0.843

AC:

28207

AN:

33480

American (AMR)

AF:

0.690

AC:

30869

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.334

AC:

8720

AN:

26130

East Asian (EAS)

AF:

0.970

AC:

38502

AN:

39700

South Asian (SAS)

AF:

0.557

AC:

48046

AN:

86256

European-Finnish (FIN)

AF:

0.493

AC:

25847

AN:

52470

Middle Eastern (MID)

AF:

0.362

AC:

2085

AN:

5766

European-Non Finnish (NFE)

AF:

0.362

AC:

402813

AN:

1111902

Other (OTH)

AF:

0.443

AC:

26765

AN:

60374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

20555

41110

61664

82219

102774

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13224

26448

39672

52896

66120

<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:

0.547

AC:

83150

AN:

152036

Hom.:

26232

Cov.:

AF XY:

0.555

AC XY:

41213

AN XY:

74314

show subpopulations

African (AFR)

AF:

0.820

AC:

33997

AN:

41476

American (AMR)

AF:

0.584

AC:

8931

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.349

AC:

1212

AN:

3472

East Asian (EAS)

AF:

0.977

AC:

5049

AN:

5168

South Asian (SAS)

AF:

0.551

AC:

2656

AN:

4824

European-Finnish (FIN)

AF:

0.486

AC:

5142

AN:

10572

Middle Eastern (MID)

AF:

0.384

AC:

112

AN:

292

European-Non Finnish (NFE)

AF:

0.365

AC:

24791

AN:

67922

Other (OTH)

AF:

0.482

AC:

1015

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1606

3213

4819

6426

8032

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

674

1348

2022

2696

3370

<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:

0.420

Hom.:

34860

Bravo

AF:

0.566

TwinsUK

AF:

0.364

AC:

1348

ALSPAC

AF:

0.353

AC:

1360

ESP6500AA

AF:

0.806

AC:

3390

ESP6500EA

AF:

0.367

AC:

3087

ExAC

AF:

0.521

AC:

62946

Asia WGS

AF:

0.764

AC:

2654

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.057

BayesDel_addAF

Benign

-0.78

BayesDel_noAF

Benign

-0.75

CADD

Benign

0.057

(source)

DANN

Benign

0.24

DEOGEN2

Benign

0.025

T;T

Eigen

Benign

-2.3

Eigen_PC

Benign

-2.3

FATHMM_MKL

Benign

0.012

LIST_S2

Benign

0.12

T;T

MetaRNN

Benign

0.0000013

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.48

.;N

PhyloP100

-0.60

PrimateAI

Benign

0.28

PROVEAN

Benign

-1.6

N;N

REVEL

Benign

0.023

Sift

Benign

1.0

T;T

Sift4G

Benign

0.29

T;T

Polyphen

0.0

B;B

Vest4

0.017

MPC

0.13

ClinPred

0.024

GERP RS

-9.6

PromoterAI

0.015

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.037

gMVP

0.11

Mutation Taster

=98/2

polymorphism (auto)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over