Variant rs2295490 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_021158.5(TRIB3):c.251A>G(p.Gln84Arg) variant causes a missense change. The variant allele was found at a frequency of 0.171 in 1,613,002 control chromosomes in the GnomAD database, including 26,855 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.16 ( 2264 hom., cov: 33)

Exomes 𝑓: 0.17 ( 24591 hom. )

Consequence

TRIB3
NM_021158.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.05

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004573077).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.359 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIB3	NM_021158.5 linkuse as main transcript	c.251A>G	p.Gln84Arg	missense_variant	2/4	ENST00000217233.9	NP_066981.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
TRIB3	ENST00000217233.9 linkuse as main transcript	c.251A>G	p.Gln84Arg	missense_variant	2/4	1	NM_021158.5	ENSP00000217233	P1
TRIB3	ENST00000422053.3 linkuse as main transcript	c.332A>G	p.Gln111Arg	missense_variant	3/5	2		ENSP00000415416
TRIB3	ENST00000449710.5 linkuse as main transcript	c.251A>G	p.Gln84Arg	missense_variant	2/4	5		ENSP00000391873
TRIB3	ENST00000615226.4 linkuse as main transcript	c.251A>G	p.Gln84Arg	missense_variant	4/5	3		ENSP00000478194

Frequencies

GnomAD3 genomes

AF:

0.165

AC:

25080

AN:

152134

Hom.:

2257

Cov.:

show subpopulations

Gnomad AFR

AF:

0.165

Gnomad AMI

AF:

0.120

Gnomad AMR

AF:

0.107

Gnomad ASJ

AF:

0.218

Gnomad EAS

AF:

0.196

Gnomad SAS

AF:

0.372

Gnomad FIN

AF:

0.192

Gnomad MID

AF:

0.203

Gnomad NFE

AF:

0.155

Gnomad OTH

AF:

0.145

GnomAD3 exomes

AF:

0.178

AC:

44325

AN:

248822

Hom.:

4917

AF XY:

0.191

AC XY:

25770

AN XY:

134920

show subpopulations

Gnomad AFR exome

AF:

0.162

Gnomad AMR exome

AF:

0.0782

Gnomad ASJ exome

AF:

0.222

Gnomad EAS exome

AF:

0.192

Gnomad SAS exome

AF:

0.383

Gnomad FIN exome

AF:

0.183

Gnomad NFE exome

AF:

0.149

Gnomad OTH exome

AF:

0.167

GnomAD4 exome

AF:

0.172

AC:

251193

AN:

1460750

Hom.:

24591

Cov.:

AF XY:

0.178

AC XY:

129639

AN XY:

726694

show subpopulations

Gnomad4 AFR exome

AF:

0.164

Gnomad4 AMR exome

AF:

0.0810

Gnomad4 ASJ exome

AF:

0.227

Gnomad4 EAS exome

AF:

0.207

Gnomad4 SAS exome

AF:

0.382

Gnomad4 FIN exome

AF:

0.178

Gnomad4 NFE exome

AF:

0.156

Gnomad4 OTH exome

AF:

0.188

GnomAD4 genome

AF:

0.165

AC:

25109

AN:

152252

Hom.:

2264

Cov.:

AF XY:

0.168

AC XY:

12489

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.165

Gnomad4 AMR

AF:

0.107

Gnomad4 ASJ

AF:

0.218

Gnomad4 EAS

AF:

0.196

Gnomad4 SAS

AF:

0.373

Gnomad4 FIN

AF:

0.192

Gnomad4 NFE

AF:

0.155

Gnomad4 OTH

AF:

0.146

Alfa

AF:

0.155

Hom.:

2855

Bravo

AF:

0.152

TwinsUK

AF:

0.155

AC:

576

ALSPAC

AF:

0.152

AC:

586

ESP6500AA

AF:

0.160

AC:

706

ESP6500EA

AF:

0.155

AC:

1334

ExAC

AF:

0.181

AC:

21957

Asia WGS

AF:

0.256

AC:

888

AN:

3478

EpiCase

AF:

0.153

EpiControl

AF:

0.154

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.046

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Benign

0.15

DEOGEN2

Benign

0.24

T;T;.;.

Eigen

Benign

-0.84

Eigen_PC

Benign

-0.60

FATHMM_MKL

Benign

0.074

LIST_S2

Benign

0.12

T;T;T;T

MetaRNN

Benign

0.0046

T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-1.6

.;N;.;.

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.45

PROVEAN

Benign

2.1

.;N;N;N

REVEL

Benign

0.078

Sift

Benign

1.0

.;T;T;T

Sift4G

Benign

1.0

T;T;T;T

Polyphen

0.0

.;B;.;.

Vest4

0.050, 0.040

MPC

0.18

ClinPred

0.0036

GERP RS

4.5

Varity_R

0.021

gMVP

0.46

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over