Variant rs292592 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_014149.4(WDR91):c.770C>T(p.Pro257Leu) variant causes a missense change. The variant allele was found at a frequency of 0.721 in 1,613,788 control chromosomes in the GnomAD database, including 422,427 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.68 ( 35855 hom., cov: 32)

Exomes 𝑓: 0.73 ( 386572 hom. )

Consequence

WDR91
NM_014149.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.50

Variant links:

Genes affected

WDR91 (HGNC:24997): (WD repeat domain 91) Enables phosphatidylinositol 3-kinase regulator activity. Involved in early endosome to late endosome transport; regulation of cellular protein catabolic process; and regulation of phosphatidylinositol 3-kinase activity. Located in cytosol; early endosome membrane; and late endosome membrane. Is extrinsic component of endosome membrane. [provided by Alliance of Genome Resources, Apr 2022]

WDR91 links:

WDR91 (HGNC:):

WDR91 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.1990732E-6).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.781 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR91	NM_014149.4 linkuse as main transcript	c.770C>T	p.Pro257Leu	missense_variant	6/15	ENST00000354475.5	NP_054868.3	A4D1P6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDR91	ENST00000354475.5 linkuse as main transcript	c.770C>T	p.Pro257Leu	missense_variant	6/15	1	NM_014149.4	ENSP00000346466.4		A4D1P6-1
WDR91	ENST00000423565.5 linkuse as main transcript	c.665C>T	p.Pro222Leu	missense_variant	6/15	5		ENSP00000392555.1		C9J1X0

Frequencies

GnomAD3 genomes

AF:

0.680

AC:

103323

AN:

151950

Hom.:

35836

Cov.:

show subpopulations

Gnomad AFR

AF:

0.534

Gnomad AMI

AF:

0.845

Gnomad AMR

AF:

0.792

Gnomad ASJ

AF:

0.727

Gnomad EAS

AF:

0.593

Gnomad SAS

AF:

0.738

Gnomad FIN

AF:

0.734

Gnomad MID

AF:

0.761

Gnomad NFE

AF:

0.731

Gnomad OTH

AF:

0.728

GnomAD3 exomes

AF:

0.720

AC:

180594

AN:

250966

Hom.:

65712

AF XY:

0.722

AC XY:

97931

AN XY:

135672

show subpopulations

Gnomad AFR exome

AF:

0.527

Gnomad AMR exome

AF:

0.821

Gnomad ASJ exome

AF:

0.734

Gnomad EAS exome

AF:

0.582

Gnomad SAS exome

AF:

0.744

Gnomad FIN exome

AF:

0.724

Gnomad NFE exome

AF:

0.730

Gnomad OTH exome

AF:

0.729

GnomAD4 exome

AF:

0.726

AC:

1060762

AN:

1461720

Hom.:

386572

Cov.:

AF XY:

0.727

AC XY:

528299

AN XY:

727164

show subpopulations

Gnomad4 AFR exome

AF:

0.523

Gnomad4 AMR exome

AF:

0.820

Gnomad4 ASJ exome

AF:

0.731

Gnomad4 EAS exome

AF:

0.598

Gnomad4 SAS exome

AF:

0.738

Gnomad4 FIN exome

AF:

0.728

Gnomad4 NFE exome

AF:

0.732

Gnomad4 OTH exome

AF:

0.717

GnomAD4 genome

AF:

0.680

AC:

103389

AN:

152068

Hom.:

35855

Cov.:

AF XY:

0.681

AC XY:

50589

AN XY:

74328

show subpopulations

Gnomad4 AFR

AF:

0.534

Gnomad4 AMR

AF:

0.793

Gnomad4 ASJ

AF:

0.727

Gnomad4 EAS

AF:

0.592

Gnomad4 SAS

AF:

0.737

Gnomad4 FIN

AF:

0.734

Gnomad4 NFE

AF:

0.731

Gnomad4 OTH

AF:

0.730

Alfa

AF:

0.722

Hom.:

94980

Bravo

AF:

0.678

TwinsUK

AF:

0.744

AC:

2760

ALSPAC

AF:

0.727

AC:

2803

ESP6500AA

AF:

0.550

AC:

2423

ESP6500EA

AF:

0.724

AC:

6223

ExAC

AF:

0.713

AC:

86547

Asia WGS

AF:

0.690

AC:

2397

AN:

3478

EpiCase

AF:

0.729

EpiControl

AF:

0.732

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.29

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.028

T;T

Eigen

Uncertain

0.31

Eigen_PC

Uncertain

0.38

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.70

T;T

MetaRNN

Benign

0.0000012

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

.;L

PrimateAI

Uncertain

0.53

PROVEAN

Uncertain

-2.5

N;D

REVEL

Benign

0.15

Sift

Benign

0.23

T;T

Sift4G

Uncertain

0.0060

D;D

Polyphen

0.90

.;P

Vest4

0.12

MPC

0.57

ClinPred

0.014

GERP RS

5.4

Varity_R

0.14

gMVP

0.17

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over