Genetic Variant WDR77:p.Val240Leu (chr1-111442735-C-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_024102.4(WDR77):c.718G>C(p.Val240Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000138 in 1,445,602 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

WDR77
NM_024102.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.65

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.33473212).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR77	NM_024102.4 link	c.718G>C	p.Val240Leu	missense_variant	Exon 8 of 10	ENST00000235090.10	NP_077007.1	Q9BQA1-1A0A024R0H7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
WDR77	ENST00000235090.10 link	c.718G>C	p.Val240Leu	missense_variant	Exon 8 of 10	1	NM_024102.4	ENSP00000235090.5	Q9BQA1-1
WDR77	ENST00000449340.1 link	c.526G>C	p.Val176Leu	missense_variant	Exon 7 of 9	5		ENSP00000409300.1	H0Y711
WDR77	ENST00000497278.5 link	n.373G>C		non_coding_transcript_exon_variant	Exon 6 of 9	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000138

AC:

AN:

1445602

Hom.:

Cov.:

AF XY:

0.00000140

AC XY:

AN XY:

716094

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33212

American (AMR)

AF:

0.00

AC:

AN:

44030

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25870

East Asian (EAS)

AF:

0.00

AC:

AN:

39188

South Asian (SAS)

AF:

0.00

AC:

AN:

84024

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53170

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5740

European-Non Finnish (NFE)

AF:

0.00000182

AC:

AN:

1100722

Other (OTH)

AF:

0.00

AC:

AN:

59646

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

May 04, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.718G>C (p.V240L) alteration is located in exon 8 (coding exon 8) of the WDR77 gene. This alteration results from a G to C substitution at nucleotide position 718, causing the valine (V) at amino acid position 240 to be replaced by a leucine (L). 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

0.17

BayesDel_addAF

Benign

-0.066

BayesDel_noAF

Benign

-0.33

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.15

Eigen

Benign

0.077

Eigen_PC

Benign

0.21

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.91

M_CAP

Benign

0.016

MetaRNN

Benign

0.33

MetaSVM

Benign

-1.1

MutationAssessor

Benign

2.0

PhyloP100

3.7

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-0.80

REVEL

Benign

0.11

Sift

Benign

0.14

Sift4G

Benign

0.42

Polyphen

0.18

Vest4

0.42

MutPred

0.64

Loss of ubiquitination at K243 (P = 0.1139);

MVP

0.60

MPC

0.72

ClinPred

0.57

GERP RS

5.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.20

gMVP

0.24

Mutation Taster

=68/32

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

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1-111442735-C-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over