1-111442744-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_024102.4(WDR77):​c.709G>A​(p.Val237Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000029 in 1,588,526 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000017 ( 0 hom. )

Consequence

WDR77
NM_024102.4 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.02
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.10170153).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
WDR77NM_024102.4 linkuse as main transcriptc.709G>A p.Val237Ile missense_variant 8/10 ENST00000235090.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
WDR77ENST00000235090.10 linkuse as main transcriptc.709G>A p.Val237Ile missense_variant 8/101 NM_024102.4 P1Q9BQA1-1
WDR77ENST00000449340.1 linkuse as main transcriptc.520G>A p.Val174Ile missense_variant 7/95
WDR77ENST00000497278.5 linkuse as main transcriptn.364G>A non_coding_transcript_exon_variant 6/93

Frequencies

GnomAD3 genomes
AF:
0.000145
AC:
22
AN:
152212
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000482
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000453
AC:
11
AN:
242846
Hom.:
0
AF XY:
0.0000381
AC XY:
5
AN XY:
131078
show subpopulations
Gnomad AFR exome
AF:
0.000514
Gnomad AMR exome
AF:
0.0000901
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000167
AC:
24
AN:
1436314
Hom.:
0
Cov.:
30
AF XY:
0.0000211
AC XY:
15
AN XY:
709872
show subpopulations
Gnomad4 AFR exome
AF:
0.000424
Gnomad4 AMR exome
AF:
0.000138
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.14e-7
Gnomad4 OTH exome
AF:
0.0000338
GnomAD4 genome
AF:
0.000145
AC:
22
AN:
152212
Hom.:
0
Cov.:
32
AF XY:
0.0000807
AC XY:
6
AN XY:
74368
show subpopulations
Gnomad4 AFR
AF:
0.000482
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000102
Hom.:
0
Bravo
AF:
0.0000945
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000577
AC:
7

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 submitterclinical testingAmbry GeneticsApr 25, 2022The c.709G>A (p.V237I) alteration is located in exon 8 (coding exon 8) of the WDR77 gene. This alteration results from a G to A substitution at nucleotide position 709, causing the valine (V) at amino acid position 237 to be replaced by an isoleucine (I). 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
0.078
BayesDel_addAF
Benign
-0.46
T
BayesDel_noAF
Benign
-0.56
CADD
Benign
9.2
DANN
Uncertain
1.0
DEOGEN2
Benign
0.15
T
Eigen
Benign
-0.16
Eigen_PC
Benign
-0.11
FATHMM_MKL
Uncertain
0.87
D
LIST_S2
Benign
0.78
T
M_CAP
Benign
0.0081
T
MetaRNN
Benign
0.10
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.3
L
MutationTaster
Benign
1.0
D;D
PrimateAI
Benign
0.30
T
PROVEAN
Benign
-0.18
N
REVEL
Benign
0.11
Sift
Benign
0.40
T
Sift4G
Benign
0.18
T
Polyphen
0.82
P
Vest4
0.28
MVP
0.28
MPC
0.22
ClinPred
0.053
T
GERP RS
4.0
Varity_R
0.041
gMVP
0.11

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.

Other links and lift over

dbSNP: rs145078783; hg19: chr1-111985366; API