Genetic Variant NM_006058.5:c.1711C>A (chr5-151033676-G-T) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM1PM2

The NM_006058.5(TNIP1):c.1711C>A(p.Arg571Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. R571C) has been classified as Uncertain significance.

Frequency

Genomes: not found (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: 4.64

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

PM1

In a modified_residue Asymmetric dimethylarginine (size 0) in uniprot entity TNIP1_HUMAN

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.1711C>A	p.Arg571Ser	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.1711C>A	p.Arg571Ser	missense_variant	Exon 16 of 18	1	NM_006058.5	ENSP00000430760.1		Q15025-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1198146

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

578182

African (AFR)

AF:

0.00

AC:

AN:

25358

American (AMR)

AF:

0.00

AC:

AN:

19110

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16174

East Asian (EAS)

AF:

0.00

AC:

AN:

31138

South Asian (SAS)

AF:

0.00

AC:

AN:

38712

European-Finnish (FIN)

AF:

0.00

AC:

AN:

42864

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4660

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

972062

Other (OTH)

AF:

0.00

AC:

AN:

48068

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.33

BayesDel_addAF

Benign

-0.060

BayesDel_noAF

Benign

-0.32

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.24

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

Eigen

Uncertain

0.67

Eigen_PC

Uncertain

0.64

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.89

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

M_CAP

Benign

0.030

MetaRNN

Uncertain

0.59

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

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.1

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

PhyloP100

4.6

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-1.4

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

REVEL

Benign

0.19

Sift

Uncertain

0.0060

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

Sift4G

Uncertain

0.0070

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

Polyphen

1.0

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

Vest4

0.80

MutPred

0.48

.;Loss of catalytic residue at R571 (P = 0.0033);Loss of catalytic residue at R571 (P = 0.0033);Loss of catalytic residue at R571 (P = 0.0033);Loss of catalytic residue at R571 (P = 0.0033);Loss of catalytic residue at R571 (P = 0.0033);Loss of catalytic residue at R571 (P = 0.0033);

MVP

0.082

MPC

0.73

ClinPred

0.94

GERP RS

5.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.28

gMVP

0.45

Mutation Taster

=74/26

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over