Variant 5-151035022-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006058.5(TNIP1):c.1567C>G(p.Gln523Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,794 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

TNIP1
NM_006058.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.18

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.13223082).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNIP1	NM_006058.5 linkuse as main transcript	c.1567C>G	p.Gln523Glu	missense_variant	15/18	ENST00000521591.6	NP_006049.3	Q15025-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNIP1	ENST00000521591.6 linkuse as main transcript	c.1567C>G	p.Gln523Glu	missense_variant	15/18	1	NM_006058.5	ENSP00000430760.1		Q15025-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251274

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135792

show subpopulations

Gnomad AFR exome

AF:

0.0000616

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461794

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727186

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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

Oct 12, 2024

The c.1567C>G (p.Q523E) alteration is located in exon 15 (coding exon 14) of the TNIP1 gene. This alteration results from a C to G substitution at nucleotide position 1567, causing the glutamine (Q) at amino acid position 523 to be replaced by a glutamic acid (E). 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

0.10

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.27

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.19

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

Eigen

Uncertain

0.28

Eigen_PC

Uncertain

0.31

FATHMM_MKL

Uncertain

0.88

LIST_S2

Uncertain

0.89

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

M_CAP

Benign

0.019

MetaRNN

Benign

0.13

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

MetaSVM

Benign

-0.45

MutationAssessor

Uncertain

2.0

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

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-1.8

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

REVEL

Benign

0.10

Sift

Benign

0.11

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

Sift4G

Benign

0.33

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

Polyphen

0.010

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

Vest4

0.25

MutPred

0.067

.;Loss of methylation at K525 (P = 0.135);Loss of methylation at K525 (P = 0.135);Loss of methylation at K525 (P = 0.135);Loss of methylation at K525 (P = 0.135);Loss of methylation at K525 (P = 0.135);Loss of methylation at K525 (P = 0.135);Loss of methylation at K525 (P = 0.135);Loss of methylation at K525 (P = 0.135);Loss of methylation at K525 (P = 0.135);Loss of methylation at K525 (P = 0.135);

MVP

0.30

MPC

0.76

ClinPred

0.45

GERP RS

4.7

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.0

Varity_R

0.17

gMVP

0.21

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