Variant 5-151033729-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The ENST00000521591.6(TNIP1):c.1658C>T(p.Pro553Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000218 in 1,360,182 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0011 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00011 ( 0 hom. )

Consequence

TNIP1
ENST00000521591.6 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.76

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 -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0084733665).

BP6

Variant 5-151033729-G-A is Benign according to our data. Variant chr5-151033729-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 732954.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNIP1	NM_006058.5 linkuse as main transcript	c.1658C>T	p.Pro553Leu	missense_variant	16/18	ENST00000521591.6	NP_006049.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNIP1	ENST00000521591.6 linkuse as main transcript	c.1658C>T	p.Pro553Leu	missense_variant	16/18	1	NM_006058.5	ENSP00000430760	P3	Q15025-1

Frequencies

GnomAD3 genomes

AF:

0.00105

AC:

160

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00364

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:

0.0000147

Gnomad OTH

AF:

0.000480

GnomAD3 exomes

AF:

0.000394

AC:

AN:

126984

Hom.:

AF XY:

0.000280

AC XY:

AN XY:

67926

show subpopulations

Gnomad AFR exome

AF:

0.00457

Gnomad AMR exome

AF:

0.0000907

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:

0.00

Gnomad OTH exome

AF:

0.000435

GnomAD4 exome

AF:

0.000112

AC:

135

AN:

1207908

Hom.:

Cov.:

AF XY:

0.000115

AC XY:

AN XY:

582520

show subpopulations

Gnomad4 AFR exome

AF:

0.00404

Gnomad4 AMR exome

AF:

0.000158

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000254

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000102

Gnomad4 OTH exome

AF:

0.000349

GnomAD4 genome

AF:

0.00106

AC:

161

AN:

152274

Hom.:

Cov.:

AF XY:

0.000980

AC XY:

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.00366

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:

0.0000147

Gnomad4 OTH

AF:

0.000475

Alfa

AF:

0.000281

Hom.:

Bravo

AF:

0.00127

ESP6500AA

AF:

0.00363

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000427

AC:

Asia WGS

AF:

0.000866

AC:

AN:

3478

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

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.094

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.48

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.22

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

Eigen

Benign

0.13

Eigen_PC

Uncertain

0.22

FATHMM_MKL

Benign

0.70

LIST_S2

Uncertain

0.89

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

M_CAP

Benign

0.0099

MetaRNN

Benign

0.0085

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

MetaSVM

Benign

-1.1

MutationAssessor

Benign

2.0

.;.;M;M;M;M;M

MutationTaster

Benign

0.93

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

PrimateAI

Benign

0.47

PROVEAN

Uncertain

-2.8

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

REVEL

Benign

0.053

Sift

Uncertain

0.0050

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

Sift4G

Uncertain

0.031

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

Polyphen

0.077

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

Vest4

0.36

MVP

0.068

MPC

0.32

ClinPred

0.046

GERP RS

4.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.053

gMVP

0.34

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