Genetic Variant NM_006058.5:c.1601G>T (chr5-151033786-C-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_006058.5(TNIP1):c.1601G>T(p.Arg534Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,180 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R534H) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TNIP1
NM_006058.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.57

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNIP1	NM_006058.5 link	c.1601G>T	p.Arg534Leu	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.1601G>T	p.Arg534Leu	missense_variant	Exon 16 of 18	1	NM_006058.5	ENSP00000430760.1		Q15025-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1217760

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

587558

African (AFR)

AF:

0.00

AC:

AN:

25508

American (AMR)

AF:

0.00

AC:

AN:

18900

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16692

East Asian (EAS)

AF:

0.00

AC:

AN:

31050

South Asian (SAS)

AF:

0.00

AC:

AN:

39878

European-Finnish (FIN)

AF:

0.00

AC:

AN:

44124

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4754

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

987548

Other (OTH)

AF:

0.00

AC:

AN:

49306

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152180

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74338

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41436

American (AMR)

AF:

0.00

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5196

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68024

Other (OTH)

AF:

0.00

AC:

AN:

2092

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.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.31

BayesDel_addAF

Uncertain

0.038

BayesDel_noAF

Benign

-0.18

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.33

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

Eigen

Uncertain

0.52

Eigen_PC

Uncertain

0.45

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.93

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

M_CAP

Benign

0.023

MetaRNN

Uncertain

0.58

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

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.1

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

PhyloP100

2.6

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-1.8

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

REVEL

Benign

0.27

Sift

Benign

0.083

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

Sift4G

Uncertain

0.026

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

Polyphen

1.0

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

Vest4

0.75

MutPred

0.55

.;Gain of ubiquitination at K529 (P = 0.0378);Gain of ubiquitination at K529 (P = 0.0378);Gain of ubiquitination at K529 (P = 0.0378);Gain of ubiquitination at K529 (P = 0.0378);Gain of ubiquitination at K529 (P = 0.0378);Gain of ubiquitination at K529 (P = 0.0378);

MVP

0.20

MPC

0.54

ClinPred

0.97

GERP RS

5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.31

gMVP

0.59

Mutation Taster

=76/24

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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NM_006058.5:c.1601G>T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over