19-33156366-A-G

Variant summary

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

The NM_173479.4(WDR88):ā€‹c.821A>Gā€‹(p.Asn274Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000062 in 1,613,956 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 (ā˜…).

Frequency

Genomes: š‘“ 0.000033 ( 0 hom., cov: 32)
Exomes š‘“: 0.0000034 ( 0 hom. )

Consequence

WDR88
NM_173479.4 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.24
Variant links:
Genes affected
WDR88 (HGNC:26999): (WD repeat domain 88)

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=0.13929677).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
WDR88NM_173479.4 linkc.821A>G p.Asn274Ser missense_variant 7/11 ENST00000355868.4 NP_775750.3 Q6ZMY6-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
WDR88ENST00000355868.4 linkc.821A>G p.Asn274Ser missense_variant 7/112 NM_173479.4 ENSP00000348129.2 Q6ZMY6-1
WDR88ENST00000361680.6 linkc.821A>G p.Asn274Ser missense_variant 7/121 ENSP00000355148.2 Q6ZMY6-2

Frequencies

GnomAD3 genomes
AF:
0.0000329
AC:
5
AN:
152190
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000199
AC:
5
AN:
251290
Hom.:
0
AF XY:
0.0000221
AC XY:
3
AN XY:
135810
show subpopulations
Gnomad AFR exome
AF:
0.0000615
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000163
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000342
AC:
5
AN:
1461766
Hom.:
0
Cov.:
31
AF XY:
0.00000413
AC XY:
3
AN XY:
727204
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000180
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000329
AC:
5
AN:
152190
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74356
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.0000655
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000282
Hom.:
0
Bravo
AF:
0.0000264

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 GeneticsFeb 05, 2024The c.821A>G (p.N274S) alteration is located in exon 7 (coding exon 7) of the WDR88 gene. This alteration results from a A to G substitution at nucleotide position 821, causing the asparagine (N) at amino acid position 274 to be replaced by a serine (S). 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
0.073
BayesDel_addAF
Benign
-0.45
T
BayesDel_noAF
Benign
-0.62
CADD
Benign
16
DANN
Benign
0.91
DEOGEN2
Benign
0.017
.;T
Eigen
Benign
-0.43
Eigen_PC
Benign
-0.40
FATHMM_MKL
Benign
0.68
D
LIST_S2
Benign
0.71
T;T
M_CAP
Benign
0.021
T
MetaRNN
Benign
0.14
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.4
L;L
PrimateAI
Benign
0.41
T
PROVEAN
Uncertain
-2.4
N;N
REVEL
Benign
0.13
Sift
Benign
0.24
T;T
Sift4G
Benign
0.34
T;T
Polyphen
0.57
.;P
Vest4
0.15
MutPred
0.38
Gain of glycosylation at N274 (P = 0.0217);Gain of glycosylation at N274 (P = 0.0217);
MVP
0.28
MPC
0.24
ClinPred
0.088
T
GERP RS
3.5
Varity_R
0.056
gMVP
0.12

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: rs1287925072; hg19: chr19-33647272; API