19-12668409-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_016145.4(WDR83OS):​c.271G>A​(p.Val91Met) variant causes a missense change. The variant allele was found at a frequency of 0.00000992 in 1,613,496 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

WDR83OS
NM_016145.4 missense

Scores

5
9
3

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.24
Variant links:
Genes affected
WDR83OS (HGNC:30203): (WD repeat domain 83 opposite strand) Enables protein folding chaperone. Involved in protein insertion into ER membrane. Is integral component of endoplasmic reticulum membrane. [provided by Alliance of Genome Resources, Apr 2022]
WDR83 (HGNC:32672): (WD repeat domain 83) This gene encodes a member of the WD-40 protein family. The protein is proposed to function as a molecular scaffold for various multimeric protein complexes. The protein associates with several components of the extracellular signal-regulated kinase (ERK) pathway, and promotes ERK activity in response to serum or other signals. The protein also interacts with egl nine homolog 3 (EGLN3, also known as PHD3) and regulates expression of hypoxia-inducible factor 1, and has been purified as part of the spliceosome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2009]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
WDR83OSNM_016145.4 linkc.271G>A p.Val91Met missense_variant Exon 4 of 4 ENST00000596731.7 NP_057229.1 Q9Y284
WDR83NM_001099737.3 linkc.-156-99C>T intron_variant Intron 1 of 10 ENST00000418543.8 NP_001093207.1 Q9BRX9
WDR83NR_029375.2 linkn.187-99C>T intron_variant Intron 1 of 10

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
WDR83OSENST00000596731.7 linkc.271G>A p.Val91Met missense_variant Exon 4 of 4 1 NM_016145.4 ENSP00000468969.1 Q9Y284
WDR83ENST00000418543.8 linkc.-156-99C>T intron_variant Intron 1 of 10 1 NM_001099737.3 ENSP00000402653.3 Q9BRX9
ENSG00000269590ENST00000597961.1 linkc.150+719G>A intron_variant Intron 2 of 4 4 ENSP00000472710.1 M0R2P5
ENSG00000285589ENST00000648033.1 linkn.*4205G>A non_coding_transcript_exon_variant Exon 14 of 14 ENSP00000498000.1 A0A3B3IU31
ENSG00000285589ENST00000648033.1 linkn.*4205G>A 3_prime_UTR_variant Exon 14 of 14 ENSP00000498000.1 A0A3B3IU31

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152152
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000160
AC:
4
AN:
249802
Hom.:
0
AF XY:
0.0000222
AC XY:
3
AN XY:
134988
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000546
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000266
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000103
AC:
15
AN:
1461344
Hom.:
0
Cov.:
32
AF XY:
0.0000110
AC XY:
8
AN XY:
726904
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000756
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000108
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152152
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74314
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000329
Hom.:
0
Bravo
AF:
0.0000113
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000247
AC:
3

ClinVar

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

Submissions by phenotype

not provided Uncertain:1
Jun 25, 2023
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 91 of the WDR83OS protein (p.Val91Met). This variant is present in population databases (rs368657914, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with WDR83OS-related conditions. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.98
BayesDel_addAF
Uncertain
0.14
D
BayesDel_noAF
Uncertain
0.13
CADD
Pathogenic
27
DANN
Uncertain
1.0
DEOGEN2
Benign
0.074
T;T
Eigen
Pathogenic
0.73
Eigen_PC
Pathogenic
0.72
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Pathogenic
0.98
D;D
M_CAP
Uncertain
0.11
D
MetaRNN
Uncertain
0.73
D;D
MetaSVM
Benign
-0.29
T
MutationAssessor
Uncertain
2.2
M;.
PrimateAI
Pathogenic
0.84
D
REVEL
Uncertain
0.46
Sift4G
Uncertain
0.011
D;D
Polyphen
1.0
D;.
Vest4
0.80
MVP
0.32
MPC
1.0
ClinPred
0.95
D
GERP RS
5.6
RBP_binding_hub_radar
0.97
RBP_regulation_power_radar
2.7
Varity_R
0.49
gMVP
0.85

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
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: rs368657914; hg19: chr19-12779223; API