19-12668559-C-T

Variant names:

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_001099737.3(WDR83):c.-105C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000164 in 1,613,990 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00027 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00015 ( 1 hom. )

Consequence

WDR83
NM_001099737.3 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 7.31

Variant links:

Genes affected

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:

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:

ENSG00000269590 (HGNC:):

ENSG00000269590 links:

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=0.15411618).

BP6

Variant 19-12668559-C-T is Benign according to our data. Variant chr19-12668559-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3604307.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR83	NM_001099737.3 link	c.-105C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 2 of 11	ENST00000418543.8	NP_001093207.1	Q9BRX9
WDR83OS	NM_016145.4 link	c.215G>A	p.Arg72Gln	missense_variant	Exon 3 of 4	ENST00000596731.7	NP_057229.1	Q9Y284
WDR83	NM_001099737.3 link	c.-105C>T		5_prime_UTR_variant	Exon 2 of 11	ENST00000418543.8	NP_001093207.1	Q9BRX9
WDR83	NR_029375.2 link	n.238C>T		non_coding_transcript_exon_variant	Exon 2 of 11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
WDR83	ENST00000418543 link	c.-105C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 2 of 11	1	NM_001099737.3	ENSP00000402653.3	Q9BRX9
WDR83OS	ENST00000596731.7 link	c.215G>A	p.Arg72Gln	missense_variant	Exon 3 of 4	1	NM_016145.4	ENSP00000468969.1	Q9Y284
WDR83	ENST00000418543 link	c.-105C>T		5_prime_UTR_variant	Exon 2 of 11	1	NM_001099737.3	ENSP00000402653.3	Q9BRX9
ENSG00000269590	ENST00000597961.1 link	c.150+569G>A		intron_variant	Intron 2 of 4	4		ENSP00000472710.1	M0R2P5
ENSG00000285589	ENST00000648033.1 link	n.*4149G>A		non_coding_transcript_exon_variant	Exon 13 of 14			ENSP00000498000.1	A0A3B3IU31
ENSG00000285589	ENST00000648033.1 link	n.*4149G>A		3_prime_UTR_variant	Exon 13 of 14			ENSP00000498000.1	A0A3B3IU31

Frequencies

GnomAD3 genomes

AF:

0.000269

AC:

AN:

152144

Hom.:

Cov.:

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:

0.00330

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.000957

GnomAD3 exomes

AF:

0.000298

AC:

AN:

251434

Hom.:

AF XY:

0.000294

AC XY:

AN XY:

135896

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:

0.00

Gnomad FIN exome

AF:

0.00305

Gnomad NFE exome

AF:

0.0000528

Gnomad OTH exome

AF:

0.000489

GnomAD4 exome

AF:

0.000153

AC:

223

AN:

1461846

Hom.:

Cov.:

AF XY:

0.000153

AC XY:

111

AN XY:

727222

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:

0.00307

Gnomad4 NFE exome

AF:

0.0000396

Gnomad4 OTH exome

AF:

0.000248

GnomAD4 genome

AF:

0.000269

AC:

AN:

152144

Hom.:

Cov.:

AF XY:

0.000404

AC XY:

AN XY:

74332

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:

0.00330

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.000957

Alfa

AF:

0.0000605

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.000247

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Oct 21, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.87

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.29

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.29

T;T

Eigen

Pathogenic

0.74

Eigen_PC

Pathogenic

0.70

FATHMM_MKL

Uncertain

0.87

LIST_S2

Uncertain

0.93

D;D

M_CAP

Benign

0.040

MetaRNN

Benign

0.15

T;T

MetaSVM

Uncertain

-0.099

MutationAssessor

Uncertain

2.8

M;.

PrimateAI

Uncertain

0.77

REVEL

Uncertain

0.36

Sift4G

Uncertain

0.029

D;D

Polyphen

1.0

D;.

Vest4

0.88

MutPred

0.77

Loss of phosphorylation at S74 (P = 0.0705);.;

MVP

0.34

MPC

1.1

ClinPred

0.33

GERP RS

4.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.7

Varity_R

0.68

gMVP

0.83

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over