Variant 5-151052238-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_006058.5(TNIP1):c.649A>G(p.Lys217Glu) variant causes a missense change. The variant allele was found at a frequency of 0.000541 in 1,613,938 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00033 ( 2 hom. )

Consequence

TNIP1
NM_006058.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.24

Variant links:

Genes affected

TNIP1 (HGNC:16903): (TNFAIP3 interacting protein 1) This gene encodes an A20-binding protein which plays a role in autoimmunity and tissue homeostasis through the regulation of nuclear factor kappa-B activation. Mutations in this gene have been associated with psoriatic arthritis, rheumatoid arthritis, and systemic lupus erythematosus. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2011]

TNIP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006763339).

BP6

Variant 5-151052238-T-C is Benign according to our data. Variant chr5-151052238-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 729998.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNIP1	NM_006058.5 linkuse as main transcript	c.649A>G	p.Lys217Glu	missense_variant	7/18	ENST00000521591.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNIP1	ENST00000521591.6 linkuse as main transcript	c.649A>G	p.Lys217Glu	missense_variant	7/18	1	NM_006058.5	P3	Q15025-1

Frequencies

GnomAD3 genomes

AF:

0.00256

AC:

389

AN:

152080

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00903

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.000598

AC:

150

AN:

250808

Hom.:

AF XY:

0.000376

AC XY:

AN XY:

135584

show subpopulations

Gnomad AFR exome

AF:

0.00776

Gnomad AMR exome

AF:

0.000377

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000654

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000793

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000329

AC:

481

AN:

1461740

Hom.:

Cov.:

AF XY:

0.000283

AC XY:

206

AN XY:

727150

show subpopulations

Gnomad4 AFR exome

AF:

0.00914

Gnomad4 AMR exome

AF:

0.000604

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000928

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000971

Gnomad4 OTH exome

AF:

0.000464

GnomAD4 genome

AF:

0.00258

AC:

392

AN:

152198

Hom.:

Cov.:

AF XY:

0.00251

AC XY:

187

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.00908

Gnomad4 AMR

AF:

0.000457

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000599

Hom.:

Bravo

AF:

0.00297

ESP6500AA

AF:

0.00931

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000758

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.0000593

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

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.48

Cadd

Benign

Dann

Uncertain

1.0

Eigen

Benign

-0.058

Eigen_PC

Benign

0.055

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.95

D;D;D;.;.;.;.;D;D;.;D;D

M_CAP

Benign

0.0085

MetaRNN

Benign

0.0068

T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

0.91

D;D;D;D;D;D;D;D;D

PrimateAI

Benign

0.48

PROVEAN

Benign

-0.46

N;N;.;N;N;.;N;N;N;N;N;N

REVEL

Benign

0.049

Sift

Benign

0.30

T;T;.;T;T;.;T;T;T;T;T;D

Sift4G

Benign

0.34

T;T;T;T;T;T;T;T;T;T;T;.

Polyphen

0.36

.;.;.;B;.;.;B;B;.;.;.;.

Vest4

0.31

MVP

0.068

MPC

0.96

ClinPred

0.022

GERP RS

4.0

Varity_R

0.14

gMVP

0.17

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