14-63599644-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_080666.4(WDR89):​c.299G>A​(p.Arg100Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000684 in 1,461,832 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000068 ( 0 hom. )

Consequence

WDR89
NM_080666.4 missense

Scores

4
8
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.43
Variant links:
Genes affected
WDR89 (HGNC:20489): (WD repeat domain 89)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.833

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
WDR89NM_080666.4 linkuse as main transcriptc.299G>A p.Arg100Gln missense_variant 3/3 ENST00000620954.2 NP_542397.1 Q96FK6A0A024R667

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
WDR89ENST00000620954.2 linkuse as main transcriptc.299G>A p.Arg100Gln missense_variant 3/36 NM_080666.4 ENSP00000480112.1 Q96FK6
WDR89ENST00000267522.7 linkuse as main transcriptc.299G>A p.Arg100Gln missense_variant 3/31 ENSP00000267522.3 Q96FK6
WDR89ENST00000394942.2 linkuse as main transcriptc.299G>A p.Arg100Gln missense_variant 2/25 ENSP00000378399.2 Q96FK6
WDR89ENST00000554717.1 linkuse as main transcriptc.299G>A p.Arg100Gln missense_variant 4/42 ENSP00000451702.1 G3V4B8

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000796
AC:
2
AN:
251210
Hom.:
0
AF XY:
0.0000147
AC XY:
2
AN XY:
135806
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.00000684
AC:
10
AN:
1461832
Hom.:
0
Cov.:
31
AF XY:
0.00000963
AC XY:
7
AN XY:
727206
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:
0.0000116
Gnomad4 FIN exome
AF:
0.0000374
Gnomad4 NFE exome
AF:
0.00000630
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
TwinsUK
AF:
0.00
AC:
0
ALSPAC
AF:
0.000259
AC:
1
ExAC
AF:
0.00000824
AC:
1

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 GeneticsOct 04, 2024The c.299G>A (p.R100Q) alteration is located in exon 3 (coding exon 1) of the WDR89 gene. This alteration results from a G to A substitution at nucleotide position 299, causing the arginine (R) at amino acid position 100 to be replaced by a glutamine (Q). 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
-0.017
T
BayesDel_noAF
Benign
-0.17
CADD
Pathogenic
26
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.22
T;T;T;.
Eigen
Uncertain
0.30
Eigen_PC
Uncertain
0.26
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.90
.;D;.;D
M_CAP
Uncertain
0.086
D
MetaRNN
Pathogenic
0.83
D;D;D;D
MetaSVM
Benign
-0.36
T
MutationAssessor
Pathogenic
3.0
M;M;M;.
PrimateAI
Benign
0.46
T
PROVEAN
Uncertain
-3.5
D;.;D;D
REVEL
Uncertain
0.33
Sift
Uncertain
0.0070
D;.;D;D
Sift4G
Uncertain
0.013
D;D;D;.
Polyphen
0.99
D;D;D;.
Vest4
0.43
MutPred
0.71
Gain of ubiquitination at K105 (P = 0.0599);Gain of ubiquitination at K105 (P = 0.0599);Gain of ubiquitination at K105 (P = 0.0599);Gain of ubiquitination at K105 (P = 0.0599);
MVP
0.77
MPC
0.59
ClinPred
0.92
D
GERP RS
4.8
Varity_R
0.40
gMVP
0.52

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: rs769328267; hg19: chr14-64066362; API