Variant chr8-125431086-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_025195.4(TRIB1):c.184C>A(p.Pro62Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000785 in 1,389,282 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P62S) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000077 ( 0 hom. )

Consequence

TRIB1
NM_025195.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.525

Variant links:

Genes affected

TRIB1 (HGNC:16891): (tribbles pseudokinase 1) Enables mitogen-activated protein kinase kinase binding activity and protein kinase inhibitor activity. Involved in several processes, including JNK cascade; negative regulation of lipopolysaccharide-mediated signaling pathway; and regulation of protein kinase activity. Located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

TRIB1 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=0.04779601).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRIB1	NM_025195.4 linkuse as main transcript	c.184C>A	p.Pro62Thr	missense_variant	1/3	ENST00000311922.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRIB1	ENST00000311922.4 linkuse as main transcript	c.184C>A	p.Pro62Thr	missense_variant	1/3	1	NM_025195.4	P1	Q96RU8-1

Frequencies

GnomAD3 genomes

AF:

0.0000921

AC:

AN:

152016

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000725

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000524

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000989

AC:

AN:

20220

Hom.:

AF XY:

0.000160

AC XY:

AN XY:

12470

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:

0.00

Gnomad NFE exome

AF:

0.000293

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000768

AC:

AN:

1237266

Hom.:

Cov.:

AF XY:

0.0000743

AC XY:

AN XY:

605444

show subpopulations

Gnomad4 AFR exome

AF:

0.0000820

Gnomad4 AMR exome

AF:

0.000142

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000109

Gnomad4 SAS exome

AF:

0.0000691

Gnomad4 FIN exome

AF:

0.0000325

Gnomad4 NFE exome

AF:

0.0000753

Gnomad4 OTH exome

AF:

0.000118

GnomAD4 genome

AF:

0.0000921

AC:

AN:

152016

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74268

show subpopulations

Gnomad4 AFR

AF:

0.0000725

Gnomad4 AMR

AF:

0.000524

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000831

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 09, 2022

The c.184C>A (p.P62T) alteration is located in exon 1 (coding exon 1) of the TRIB1 gene. This alteration results from a C to A substitution at nucleotide position 184, causing the proline (P) at amino acid position 62 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.53

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.12

Eigen

Benign

-0.63

Eigen_PC

Benign

-0.56

FATHMM_MKL

Benign

0.28

LIST_S2

Benign

0.61

M_CAP

Uncertain

0.12

MetaRNN

Benign

0.048

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.23

MutationTaster

Benign

0.76

PrimateAI

Pathogenic

0.92

PROVEAN

Benign

-0.11

REVEL

Benign

0.024

Sift

Uncertain

0.0060

Sift4G

Benign

0.18

Polyphen

0.041

Vest4

0.17

MutPred

0.21

Gain of phosphorylation at P62 (P = 0.0103);

MVP

0.23

MPC

0.52

ClinPred

0.047

GERP RS

1.6

Varity_R

0.13

gMVP

0.35

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