Variant 19-12669365-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_016145.4(WDR83OS):c.39C>T(p.Asn13=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0646 in 1,603,230 control chromosomes in the GnomAD database, including 4,119 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.050 ( 326 hom., cov: 32)

Exomes 𝑓: 0.066 ( 3793 hom. )

Consequence

WDR83OS
NM_016145.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.13

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.6).

BP6

Variant 19-12669365-G-A is Benign according to our data. Variant chr19-12669365-G-A is described in ClinVar as [Benign]. Clinvar id is 2039025.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=2.13 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.07 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
WDR83OS	NM_016145.4 linkuse as main transcript	c.39C>T	p.Asn13=	synonymous_variant	1/4	ENST00000596731.7
WDR83	NM_001099737.3 linkuse as main transcript	c.-36-390G>A		intron_variant		ENST00000418543.8
WDR83	NR_029375.2 linkuse as main transcript	n.307-390G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WDR83OS	ENST00000596731.7 linkuse as main transcript	c.39C>T	p.Asn13=	synonymous_variant	1/4	1	NM_016145.4	P4
WDR83	ENST00000418543.8 linkuse as main transcript	c.-36-390G>A		intron_variant		1	NM_001099737.3	P1

Frequencies

GnomAD3 genomes

AF:

0.0499

AC:

7588

AN:

152172

Hom.:

326

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0151

Gnomad AMI

AF:

0.0581

Gnomad AMR

AF:

0.0246

Gnomad ASJ

AF:

0.0150

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00995

Gnomad FIN

AF:

0.140

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0717

Gnomad OTH

AF:

0.0350

GnomAD3 exomes

AF:

0.0507

AC:

11697

AN:

230570

Hom.:

457

AF XY:

0.0501

AC XY:

6252

AN XY:

124692

show subpopulations

Gnomad AFR exome

AF:

0.0147

Gnomad AMR exome

AF:

0.0179

Gnomad ASJ exome

AF:

0.0142

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0116

Gnomad FIN exome

AF:

0.143

Gnomad NFE exome

AF:

0.0713

Gnomad OTH exome

AF:

0.0529

GnomAD4 exome

AF:

0.0662

AC:

95997

AN:

1450940

Hom.:

3793

Cov.:

AF XY:

0.0643

AC XY:

46364

AN XY:

720848

show subpopulations

Gnomad4 AFR exome

AF:

0.0116

Gnomad4 AMR exome

AF:

0.0188

Gnomad4 ASJ exome

AF:

0.0142

Gnomad4 EAS exome

AF:

0.000102

Gnomad4 SAS exome

AF:

0.0119

Gnomad4 FIN exome

AF:

0.138

Gnomad4 NFE exome

AF:

0.0748

Gnomad4 OTH exome

AF:

0.0565

GnomAD4 genome

AF:

0.0498

AC:

7588

AN:

152290

Hom.:

326

Cov.:

AF XY:

0.0509

AC XY:

3789

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.0150

Gnomad4 AMR

AF:

0.0246

Gnomad4 ASJ

AF:

0.0150

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0102

Gnomad4 FIN

AF:

0.140

Gnomad4 NFE

AF:

0.0717

Gnomad4 OTH

AF:

0.0346

Alfa

AF:

0.0595

Hom.:

192

Bravo

AF:

0.0405

Asia WGS

AF:

0.00722

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 25, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Benign

0.94

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

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.

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