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GeneBe

20-396363-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_021158.5(TRIB3):c.750G>A(p.Ala250=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000796 in 1,613,538 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0034 ( 8 hom., cov: 33)
Exomes 𝑓: 0.00052 ( 3 hom. )

Consequence

TRIB3
NM_021158.5 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.13
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 20-396363-G-A is Benign according to our data. Variant chr20-396363-G-A is described in ClinVar as [Benign]. Clinvar id is 733898.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-1.13 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 521 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
TRIB3NM_021158.5 linkuse as main transcriptc.750G>A p.Ala250= synonymous_variant 4/4 ENST00000217233.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TRIB3ENST00000217233.9 linkuse as main transcriptc.750G>A p.Ala250= synonymous_variant 4/41 NM_021158.5 P1
TRIB3ENST00000422053.3 linkuse as main transcriptc.831G>A p.Ala277= synonymous_variant 5/52
TRIB3ENST00000449710.5 linkuse as main transcriptc.750G>A p.Ala250= synonymous_variant 4/45

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00342
AC:
521
AN:
152240
Hom.:
8
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0118
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000720
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.000847
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000176
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000985
AC:
247
AN:
250748
Hom.:
4
AF XY:
0.000855
AC XY:
116
AN XY:
135674
show subpopulations
Gnomad AFR exome
AF:
0.0106
Gnomad AMR exome
AF:
0.000174
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000109
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.000421
Gnomad NFE exome
AF:
0.000511
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000521
AC:
762
AN:
1461180
Hom.:
3
Cov.:
31
AF XY:
0.000497
AC XY:
361
AN XY:
726950
show subpopulations
Gnomad4 AFR exome
AF:
0.0121
Gnomad4 AMR exome
AF:
0.000291
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000504
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.000493
Gnomad4 NFE exome
AF:
0.000248
Gnomad4 OTH exome
AF:
0.000629
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00343
AC:
523
AN:
152358
Hom.:
8
Cov.:
33
AF XY:
0.00349
AC XY:
260
AN XY:
74504
show subpopulations
Gnomad4 AFR
AF:
0.0118
Gnomad4 AMR
AF:
0.000719
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.000847
Gnomad4 NFE
AF:
0.000176
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.00212
Hom.:
0
Bravo
AF:
0.00383
Asia WGS
AF:
0.000577
AC:
3
AN:
3478
EpiCase
AF:
0.000164
EpiControl
AF:
0.000415

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 submitterclinical testingInvitaeDec 13, 2017- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.81
Cadd
Benign
1.7
Dann
Benign
0.91
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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.

Other links and lift over

dbSNP: rs73565400; hg19: chr20-377007; COSMIC: COSV53931164; COSMIC: COSV53931164; API