19-33132368-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_173479.4(WDR88):​c.199C>T​(p.Pro67Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000041 in 1,461,840 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 (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

WDR88
NM_173479.4 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -3.54
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 Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.04051143).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
WDR88NM_173479.4 linkc.199C>T p.Pro67Ser missense_variant Exon 1 of 11 ENST00000355868.4 NP_775750.3 Q6ZMY6-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
WDR88ENST00000355868.4 linkc.199C>T p.Pro67Ser missense_variant Exon 1 of 11 2 NM_173479.4 ENSP00000348129.2 Q6ZMY6-1
WDR88ENST00000361680.6 linkc.199C>T p.Pro67Ser missense_variant Exon 1 of 12 1 ENSP00000355148.2 Q6ZMY6-2
WDR88ENST00000592765.5 linkc.199C>T p.Pro67Ser missense_variant Exon 1 of 6 5 ENSP00000467383.1 K7EPH1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000410
AC:
6
AN:
1461840
Hom.:
0
Cov.:
31
AF XY:
0.00000413
AC XY:
3
AN XY:
727230
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
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:
0.00000540
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Dec 21, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.199C>T (p.P67S) alteration is located in exon 1 (coding exon 1) of the WDR88 gene. This alteration results from a C to T substitution at nucleotide position 199, causing the proline (P) at amino acid position 67 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
0.074
BayesDel_addAF
Benign
-0.28
T
BayesDel_noAF
Benign
-0.65
CADD
Benign
0.0010
DANN
Benign
0.85
DEOGEN2
Benign
0.00096
.;.;T
Eigen
Benign
-1.7
Eigen_PC
Benign
-1.8
FATHMM_MKL
Benign
0.0073
N
LIST_S2
Benign
0.43
T;T;T
M_CAP
Benign
0.011
T
MetaRNN
Benign
0.041
T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.20
.;N;N
PrimateAI
Benign
0.25
T
PROVEAN
Benign
0.42
.;N;N
REVEL
Benign
0.036
Sift
Benign
1.0
.;T;T
Sift4G
Benign
0.92
T;T;T
Polyphen
0.0
.;.;B
Vest4
0.16
MutPred
0.39
Loss of catalytic residue at P67 (P = 0.0076);Loss of catalytic residue at P67 (P = 0.0076);Loss of catalytic residue at P67 (P = 0.0076);
MVP
0.067
MPC
0.26
ClinPred
0.074
T
GERP RS
-4.0
Varity_R
0.016
gMVP
0.060

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-33623274; COSMIC: COSV99404341; COSMIC: COSV99404341; API