Genetic Variant WDR93:p.Ser254Thr (chr15-89716914-T-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_020212.2(WDR93):c.760T>A(p.Ser254Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.426 in 1,555,692 control chromosomes in the GnomAD database, including 145,383 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 0.42 ( 14008 hom., cov: 32)

Exomes 𝑓: 0.43 ( 131375 hom. )

Consequence

WDR93
NM_020212.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.440

Publications

29 publications found

Variant links:

Genes affected

WDR93 (HGNC:26924): (WD repeat domain 93) Predicted to enable oxidoreductase activity, acting on NAD(P)H. Predicted to be involved in electron transport chain. Predicted to be part of mitochondrial respiratory chain complex I. [provided by Alliance of Genome Resources, Apr 2022]

WDR93 Gene-Disease associations (from GenCC):

autism spectrum disorder
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

WDR93 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=1.1756467E-4).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.479 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR93	NM_020212.2 link	c.760T>A	p.Ser254Thr	missense_variant	Exon 7 of 17	ENST00000268130.12	NP_064597.1	Q6P2C0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDR93	ENST00000268130.12 link	c.760T>A	p.Ser254Thr	missense_variant	Exon 7 of 17	1	NM_020212.2	ENSP00000268130.7		Q6P2C0-1
WDR93	ENST00000560294.5 link	c.760T>A	p.Ser254Thr	missense_variant	Exon 7 of 17	2		ENSP00000453971.1		Q6P2C0-2

Frequencies

GnomAD3 genomes

AF:

0.421

AC:

63953

AN:

151866

Hom.:

13991

Cov.:

show subpopulations

Gnomad AFR

AF:

0.485

Gnomad AMI

AF:

0.666

Gnomad AMR

AF:

0.331

Gnomad ASJ

AF:

0.450

Gnomad EAS

AF:

0.214

Gnomad SAS

AF:

0.412

Gnomad FIN

AF:

0.273

Gnomad MID

AF:

0.373

Gnomad NFE

AF:

0.438

Gnomad OTH

AF:

0.398

GnomAD2 exomes

AF:

0.377

AC:

83817

AN:

222306

AF XY:

0.384

show subpopulations

Gnomad AFR exome

AF:

0.476

Gnomad AMR exome

AF:

0.243

Gnomad ASJ exome

AF:

0.443

Gnomad EAS exome

AF:

0.194

Gnomad FIN exome

AF:

0.281

Gnomad NFE exome

AF:

0.434

Gnomad OTH exome

AF:

0.385

GnomAD4 exome

AF:

0.427

AC:

598829

AN:

1403710

Hom.:

131375

Cov.:

AF XY:

0.426

AC XY:

297563

AN XY:

697730

show subpopulations

African (AFR)

AF:

0.475

AC:

14509

AN:

30576

American (AMR)

AF:

0.257

AC:

9904

AN:

38528

Ashkenazi Jewish (ASJ)

AF:

0.439

AC:

11114

AN:

25330

East Asian (EAS)

AF:

0.229

AC:

8534

AN:

37222

South Asian (SAS)

AF:

0.410

AC:

31310

AN:

76402

European-Finnish (FIN)

AF:

0.292

AC:

15474

AN:

53032

Middle Eastern (MID)

AF:

0.412

AC:

2323

AN:

5634

European-Non Finnish (NFE)

AF:

0.446

AC:

481496

AN:

1078870

Other (OTH)

AF:

0.416

AC:

24165

AN:

58116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.453

Heterozygous variant carriers

14602

29204

43805

58407

73009

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14368

28736

43104

57472

71840

<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:

0.421

AC:

64023

AN:

151982

Hom.:

14008

Cov.:

AF XY:

0.411

AC XY:

30569

AN XY:

74298

show subpopulations

African (AFR)

AF:

0.485

AC:

20095

AN:

41442

American (AMR)

AF:

0.331

AC:

5052

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.450

AC:

1560

AN:

3468

East Asian (EAS)

AF:

0.215

AC:

1115

AN:

5178

South Asian (SAS)

AF:

0.411

AC:

1979

AN:

4810

European-Finnish (FIN)

AF:

0.273

AC:

2883

AN:

10550

Middle Eastern (MID)

AF:

0.391

AC:

115

AN:

294

European-Non Finnish (NFE)

AF:

0.438

AC:

29783

AN:

67958

Other (OTH)

AF:

0.397

AC:

834

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1860

3721

5581

7442

9302

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

594

1188

1782

2376

2970

<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:

0.430

Hom.:

11198

Bravo

AF:

0.425

TwinsUK

AF:

0.465

AC:

1726

ALSPAC

AF:

0.447

AC:

1721

ESP6500AA

AF:

0.471

AC:

2074

ESP6500EA

AF:

0.441

AC:

3788

ExAC

AF:

0.391

AC:

47502

Asia WGS

AF:

0.341

AC:

1191

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

-0.84

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.090

(source)

DANN

Benign

0.36

DEOGEN2

Benign

0.0016

T;.

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.00029

LIST_S2

Benign

0.13

T;T

MetaRNN

Benign

0.00012

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-0.95

N;N

PhyloP100

-0.44

PrimateAI

Benign

0.35

PROVEAN

Benign

1.4

N;N

REVEL

Benign

0.020

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0

B;B

Vest4

0.014

MPC

0.065

ClinPred

0.0027

GERP RS

-2.3

Varity_R

0.043

gMVP

0.16

Mutation Taster

=100/0

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