5-151033642-G-A

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_006058.5(TNIP1):c.1745C>T(p.Pro582Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000014 in 1,360,012 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. P582P) has been classified as Benign.

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 29)

Exomes 𝑓: 0.0000091 ( 0 hom. )

Consequence

TNIP1
NM_006058.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.97

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

systemic lupus erythematosus
Inheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet

TNIP1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06467444).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNIP1	NM_006058.5 link	c.1745C>T	p.Pro582Leu	missense_variant	Exon 16 of 18	ENST00000521591.6	NP_006049.3	Q15025-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNIP1	ENST00000521591.6 link	c.1745C>T	p.Pro582Leu	missense_variant	Exon 16 of 18	1	NM_006058.5	ENSP00000430760.1		Q15025-1

Frequencies

GnomAD3 genomes

AF:

0.0000527

AC:

AN:

151886

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000967

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000417

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000330

AC:

AN:

121242

AF XY:

0.0000451

show subpopulations

Gnomad AFR exome

AF:

0.000105

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS 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:

0.00000911

AC:

AN:

1208008

Hom.:

Cov.:

AF XY:

0.00000685

AC XY:

AN XY:

583758

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25642

American (AMR)

AF:

0.000152

AC:

AN:

19770

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16350

East Asian (EAS)

AF:

0.00

AC:

AN:

31372

South Asian (SAS)

AF:

0.000121

AC:

AN:

41370

European-Finnish (FIN)

AF:

0.00

AC:

AN:

43054

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4620

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

977276

Other (OTH)

AF:

0.0000618

AC:

AN:

48554

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.534

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000526

AC:

AN:

152004

Hom.:

Cov.:

AF XY:

0.0000807

AC XY:

AN XY:

74306

show subpopulations

African (AFR)

AF:

0.0000964

AC:

AN:

41480

American (AMR)

AF:

0.000131

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5148

South Asian (SAS)

AF:

0.000417

AC:

AN:

4796

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67914

Other (OTH)

AF:

0.00

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ExAC

AF:

0.0000425

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Sep 26, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.1745C>T (p.P582L) alteration is located in exon 16 (coding exon 15) of the TNIP1 gene. This alteration results from a C to T substitution at nucleotide position 1745, causing the proline (P) at amino acid position 582 to be replaced by a leucine (L). 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

0.077

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.50

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.18

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

Eigen

Benign

0.029

Eigen_PC

Benign

0.13

FATHMM_MKL

Benign

0.76

LIST_S2

Uncertain

0.89

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

M_CAP

Benign

0.0094

MetaRNN

Benign

0.065

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

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

.;.;L;L;L;L;L

PhyloP100

3.0

PrimateAI

Benign

0.42

PROVEAN

Benign

-1.4

N;N;N;N;N;N;N

REVEL

Benign

0.035

Sift

Uncertain

0.011

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

Sift4G

Benign

0.54

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

Polyphen

0.17

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

Vest4

0.47

MutPred

0.32

.;Loss of glycosylation at P582 (P = 0.0296);Loss of glycosylation at P582 (P = 0.0296);Loss of glycosylation at P582 (P = 0.0296);Loss of glycosylation at P582 (P = 0.0296);Loss of glycosylation at P582 (P = 0.0296);Loss of glycosylation at P582 (P = 0.0296);

MVP

0.068

MPC

0.29

ClinPred

0.13

GERP RS

3.2

Varity_R

0.049

gMVP

0.28

Mutation Taster

=84/16

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

5-151033642-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over