Variant 1-111449144-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_024102.4(WDR77):c.26T>G(p.Leu9Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000091 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00031 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

WDR77
NM_024102.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.325

Variant links:

Genes affected

WDR77 (HGNC:29652): (WD repeat domain 77) The protein encoded by this gene is an androgen receptor coactivator that forms a complex with protein arginine methyltransferase 5, which modifies specific arginines to dimethylarginines in several spliceosomal Sm proteins. The encoded protein may be involved in the early stages of prostate cancer, with most of the protein being nuclear-localized in benign cells but cytoplasmic in cancer cells. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2015]

WDR77 links:

WDR77 (HGNC:):

WDR77 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.104287565).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR77	NM_024102.4 linkuse as main transcript	c.26T>G	p.Leu9Arg	missense_variant	1/10	ENST00000235090.10	NP_077007.1	Q9BQA1-1A0A024R0H7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDR77	ENST00000235090.10 linkuse as main transcript	c.26T>G	p.Leu9Arg	missense_variant	1/10	1	NM_024102.4	ENSP00000235090.5		Q9BQA1-1
ATP5PB	ENST00000493119.5 linkuse as main transcript	n.87-51A>C		intron_variant		3

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

142588

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0000526

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000631

Gnomad SAS

AF:

0.000445

Gnomad FIN

AF:

0.000324

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000461

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000307

AC:

420

AN:

1366302

Hom.:

Cov.:

AF XY:

0.000281

AC XY:

191

AN XY:

679472

show subpopulations

Gnomad4 AFR exome

AF:

0.000521

Gnomad4 AMR exome

AF:

0.000297

Gnomad4 ASJ exome

AF:

0.000699

Gnomad4 EAS exome

AF:

0.000756

Gnomad4 SAS exome

AF:

0.0000480

Gnomad4 FIN exome

AF:

0.00253

Gnomad4 NFE exome

AF:

0.000212

Gnomad4 OTH exome

AF:

0.000510

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000911

AC:

AN:

142678

Hom.:

Cov.:

AF XY:

0.0000860

AC XY:

AN XY:

69774

show subpopulations

Gnomad4 AFR

AF:

0.0000524

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000632

Gnomad4 SAS

AF:

0.000445

Gnomad4 FIN

AF:

0.000324

Gnomad4 NFE

AF:

0.0000461

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 03, 2023

The c.26T>G (p.L9R) alteration is located in exon 1 (coding exon 1) of the WDR77 gene. This alteration results from a T to G substitution at nucleotide position 26, causing the leucine (L) at amino acid position 9 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.073

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.23

Eigen

Benign

-0.94

Eigen_PC

Benign

-0.89

FATHMM_MKL

Benign

0.060

LIST_S2

Benign

0.78

M_CAP

Benign

0.0097

MetaRNN

Benign

0.10

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-1.3

REVEL

Benign

0.051

Sift

Uncertain

0.020

Sift4G

Benign

0.24

Polyphen

0.0050

Vest4

0.18

MutPred

0.33

Gain of MoRF binding (P = 0.0252);

MVP

0.65

MPC

0.41

ClinPred

0.084

GERP RS

2.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.30

gMVP

0.70

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over