Genetic Variant WDR83OS:p.Lys78Asn (chr19-12668540-C-G) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_016145.4(WDR83OS):c.234G>C(p.Lys78Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. K78K) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Consequence

WDR83OS
NM_016145.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.277

Publications

0 publications found

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]

WDR83OS links:

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]

WDR83 links:

ENSG00000269590 (HGNC:):

ENSG00000269590 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.802

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016145.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
WDR83OS	NM_016145.4	MANE Select	c.234G>C	p.Lys78Asn	missense	Exon 3 of 4	NP_057229.1	Q9Y284
WDR83	NM_001099737.3	MANE Select	c.-124C>G		5_prime_UTR	Exon 2 of 11	NP_001093207.1	Q9BRX9
WDR83	NR_029375.2		n.219C>G		non_coding_transcript_exon	Exon 2 of 11

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
WDR83OS	ENST00000596731.7	TSL:1 MANE Select	c.234G>C	p.Lys78Asn	missense	Exon 3 of 4	ENSP00000468969.1	Q9Y284
WDR83	ENST00000418543.8	TSL:1 MANE Select	c.-124C>G		5_prime_UTR	Exon 2 of 11	ENSP00000402653.3	Q9BRX9
ENSG00000269590	ENST00000597961.1	TSL:4	c.150+588G>C		intron	N/A	ENSP00000472710.1	M0R2P5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

1.0

BayesDel_addAF

Benign

-0.015

BayesDel_noAF

Benign

-0.26

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.26

Eigen

Uncertain

0.25

Eigen_PC

Benign

0.11

FATHMM_MKL

Benign

0.51

LIST_S2

Uncertain

0.94

M_CAP

Uncertain

0.10

MetaRNN

Pathogenic

0.80

MetaSVM

Benign

-0.37

MutationAssessor

Pathogenic

3.1

PhyloP100

-0.28

PrimateAI

Pathogenic

0.84

REVEL

Uncertain

0.40

Sift4G

Uncertain

0.0050

Polyphen

1.0

Vest4

0.81

MutPred

0.70

Loss of ubiquitination at K78 (P = 0.0039)

MVP

0.27

MPC

1.1

ClinPred

0.96

GERP RS

1.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.7

Varity_R

0.97

gMVP

0.96

Mutation Taster

=28/72

disease causing

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over