Variant 20-391432-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_021158.5(TRIB3):c.437G>A(p.Ser146Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0074 in 1,613,908 control chromosomes in the GnomAD database, including 80 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0050 ( 3 hom., cov: 33)

Exomes 𝑓: 0.0077 ( 77 hom. )

Consequence

TRIB3
NM_021158.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.76

Variant links:

Genes affected

TRIB3 (HGNC:16228): (tribbles pseudokinase 3) The protein encoded by this gene is a putative protein kinase that is induced by the transcription factor NF-kappaB. The encoded protein is a negative regulator of NF-kappaB and can also sensitize cells to TNF- and TRAIL-induced apoptosis. In addition, this protein can negatively regulate the cell survival serine-threonine kinase AKT1. Differential promoter usage and alternate splicing result in multiple transcript variants. [provided by RefSeq, Jul 2014]

TRIB3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.010254204).

BP6

Variant 20-391432-G-A is Benign according to our data. Variant chr20-391432-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3024848.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 761 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIB3	NM_021158.5 linkuse as main transcript	c.437G>A	p.Ser146Asn	missense_variant	3/4	ENST00000217233.9	NP_066981.2	Q96RU7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TRIB3	ENST00000217233.9 linkuse as main transcript	c.437G>A	p.Ser146Asn	missense_variant	3/4	1	NM_021158.5	ENSP00000217233.3	Q96RU7
TRIB3	ENST00000422053.3 linkuse as main transcript	c.518G>A	p.Ser173Asn	missense_variant	4/5	2		ENSP00000415416.2	J3KR25
TRIB3	ENST00000449710.5 linkuse as main transcript	c.437G>A	p.Ser146Asn	missense_variant	3/4	5		ENSP00000391873.2	B0QYQ2
TRIB3	ENST00000615226.4 linkuse as main transcript	c.*46G>A		downstream_gene_variant		3		ENSP00000478194.2	A0A087WTX3

Frequencies

GnomAD3 genomes

AF:

0.00500

AC:

761

AN:

152240

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00142

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00635

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000577

Gnomad SAS

AF:

0.00186

Gnomad FIN

AF:

0.000282

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00845

Gnomad OTH

AF:

0.00669

GnomAD3 exomes

AF:

0.00483

AC:

1210

AN:

250300

Hom.:

AF XY:

0.00493

AC XY:

668

AN XY:

135540

show subpopulations

Gnomad AFR exome

AF:

0.00105

Gnomad AMR exome

AF:

0.00307

Gnomad ASJ exome

AF:

0.000199

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00212

Gnomad FIN exome

AF:

0.000418

Gnomad NFE exome

AF:

0.00864

Gnomad OTH exome

AF:

0.00540

GnomAD4 exome

AF:

0.00765

AC:

11183

AN:

1461550

Hom.:

Cov.:

AF XY:

0.00743

AC XY:

5399

AN XY:

727080

show subpopulations

Gnomad4 AFR exome

AF:

0.00131

Gnomad4 AMR exome

AF:

0.00302

Gnomad4 ASJ exome

AF:

0.000115

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00214

Gnomad4 FIN exome

AF:

0.000564

Gnomad4 NFE exome

AF:

0.00932

Gnomad4 OTH exome

AF:

0.00656

GnomAD4 genome

AF:

0.00499

AC:

761

AN:

152358

Hom.:

Cov.:

AF XY:

0.00454

AC XY:

338

AN XY:

74504

show subpopulations

Gnomad4 AFR

AF:

0.00142

Gnomad4 AMR

AF:

0.00634

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000578

Gnomad4 SAS

AF:

0.00186

Gnomad4 FIN

AF:

0.000282

Gnomad4 NFE

AF:

0.00845

Gnomad4 OTH

AF:

0.00662

Alfa

AF:

0.00771

Hom.:

Bravo

AF:

0.00538

TwinsUK

AF:

0.00782

AC:

ALSPAC

AF:

0.00778

AC:

ESP6500AA

AF:

0.00159

AC:

ESP6500EA

AF:

0.0101

AC:

ExAC

AF:

0.00471

AC:

572

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00878

EpiControl

AF:

0.00836

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2024

TRIB3: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.48

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.29

T;.;.

Eigen

Uncertain

0.59

Eigen_PC

Uncertain

0.57

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.85

T;D;T

MetaRNN

Benign

0.010

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

L;.;.

PrimateAI

Uncertain

0.57

PROVEAN

Uncertain

-2.5

D;D;D

REVEL

Benign

0.12

Sift

Uncertain

0.014

D;D;D

Sift4G

Uncertain

0.050

T;D;D

Polyphen

1.0

D;.;.

Vest4

0.25

MVP

0.66

MPC

0.48

ClinPred

0.017

GERP RS

5.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.44

gMVP

0.31

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