5-151033634-G-A

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006058.5(TNIP1):c.1753C>T(p.Leu585Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 0.0000016 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TNIP1
NM_006058.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.08

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: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.10574511).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNIP1	NM_006058.5 link	c.1753C>T	p.Leu585Phe	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.1753C>T	p.Leu585Phe	missense_variant	Exon 16 of 18	1	NM_006058.5	ENSP00000430760.1		Q15025-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000813

AC:

AN:

123074

AF XY:

0.0000148

show subpopulations

Gnomad AFR exome

AF:

0.00

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:

0.0000160

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000164

AC:

AN:

1221238

Hom.:

Cov.:

AF XY:

0.00000169

AC XY:

AN XY:

591130

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

25898

American (AMR)

AF:

0.0000489

AC:

AN:

20466

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16640

East Asian (EAS)

AF:

0.00

AC:

AN:

31714

South Asian (SAS)

AF:

0.00

AC:

AN:

44584

European-Finnish (FIN)

AF:

0.00

AC:

AN:

43856

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4690

European-Non Finnish (NFE)

AF:

0.00000102

AC:

AN:

984118

Other (OTH)

AF:

0.00

AC:

AN:

49272

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000203), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.375

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.00000850

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Mar 15, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.1753C>T (p.L585F) 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 1753, causing the leucine (L) at amino acid position 585 to be replaced by a phenylalanine (F). 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

0.074

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.63

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.11

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

Eigen

Benign

-0.082

Eigen_PC

Benign

-0.057

FATHMM_MKL

Benign

0.58

LIST_S2

Benign

0.81

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

M_CAP

Benign

0.0052

MetaRNN

Benign

0.11

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

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

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

PhyloP100

1.1

PrimateAI

Benign

0.37

PROVEAN

Benign

-0.70

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

REVEL

Benign

0.054

Sift

Benign

0.099

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

Sift4G

Benign

0.26

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

Polyphen

0.77

.;.;P;.;P;P;.

Vest4

0.25

MutPred

0.17

.;Loss of catalytic residue at L585 (P = 0.0921);Loss of catalytic residue at L585 (P = 0.0921);Loss of catalytic residue at L585 (P = 0.0921);Loss of catalytic residue at L585 (P = 0.0921);Loss of catalytic residue at L585 (P = 0.0921);Loss of catalytic residue at L585 (P = 0.0921);

MVP

0.17

MPC

0.67

ClinPred

0.36

GERP RS

3.0

Varity_R

0.026

gMVP

0.15

Mutation Taster

=94/6

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over