16-650662-G-C

Variant summary

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

The NM_145294.5(WDR90):ā€‹c.512G>Cā€‹(p.Ser171Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000447 in 1,612,526 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‘“ 0.000039 ( 0 hom., cov: 33)
Exomes š‘“: 0.000045 ( 0 hom. )

Consequence

WDR90
NM_145294.5 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.600
Variant links:
Genes affected
WDR90 (HGNC:26960): (WD repeat domain 90) Involved in cilium assembly. Located in centriole. [provided by Alliance of Genome Resources, Apr 2022]

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=0.092541754).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
WDR90NM_145294.5 linkc.512G>C p.Ser171Thr missense_variant 5/41 ENST00000293879.9 NP_660337.3 Q96KV7-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
WDR90ENST00000293879.9 linkc.512G>C p.Ser171Thr missense_variant 5/415 NM_145294.5 ENSP00000293879.4 Q96KV7-1

Frequencies

GnomAD3 genomes
AF:
0.0000394
AC:
6
AN:
152196
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00115
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000443
AC:
11
AN:
248208
Hom.:
0
AF XY:
0.0000370
AC XY:
5
AN XY:
135146
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.000700
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000356
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000452
AC:
66
AN:
1460330
Hom.:
0
Cov.:
33
AF XY:
0.0000496
AC XY:
36
AN XY:
726418
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.000804
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000369
Gnomad4 OTH exome
AF:
0.0000663
GnomAD4 genome
AF:
0.0000394
AC:
6
AN:
152196
Hom.:
0
Cov.:
33
AF XY:
0.0000403
AC XY:
3
AN XY:
74364
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00115
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000565
Hom.:
0
Bravo
AF:
0.0000642
ExAC
AF:
0.0000331
AC:
4
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

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 GeneticsJun 25, 2024The c.512G>C (p.S171T) alteration is located in exon 5 (coding exon 5) of the WDR90 gene. This alteration results from a G to C substitution at nucleotide position 512, causing the serine (S) at amino acid position 171 to be replaced by a threonine (T). 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
0.20
BayesDel_addAF
Benign
-0.35
T
BayesDel_noAF
Benign
-0.63
CADD
Benign
17
DANN
Benign
0.94
DEOGEN2
Benign
0.030
T;T
Eigen
Benign
-0.088
Eigen_PC
Benign
-0.17
FATHMM_MKL
Benign
0.75
D
LIST_S2
Benign
0.82
T;T
M_CAP
Benign
0.020
T
MetaRNN
Benign
0.093
T;T
MetaSVM
Benign
-0.97
T
MutationAssessor
Benign
2.0
.;M
PrimateAI
Benign
0.29
T
PROVEAN
Benign
-1.5
N;N
REVEL
Benign
0.14
Sift
Benign
0.030
D;D
Sift4G
Benign
0.15
T;T
Polyphen
0.67
.;P
Vest4
0.26
MutPred
0.66
Gain of helix (P = 0.0325);Gain of helix (P = 0.0325);
MVP
0.13
MPC
0.24
ClinPred
0.20
T
GERP RS
-1.7
Varity_R
0.12
gMVP
0.13

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs201099087; hg19: chr16-700662; API