5-151033675-C-T

Variant names:

• chr5-151033675-C-T
• rs1168947768
• NM_006058.5:c.1712G>A

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM1 PM2

The NM_006058.5(TNIP1):​c.1712G>A​(p.Arg571His) variant causes a missense change. The variant allele was found at a frequency of 0.0000149 in 1,345,118 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). 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: 𝑓 0.000040 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: TNIP1 NM_006058.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.77
• Publications: 1 publications found

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

ACMG classification

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	c.1712G>A	p.Arg571His	missense_variant	Exon 16 of 18	ENST00000521591.6	NP_006049.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNIP1	ENST00000521591.6	c.1712G>A	p.Arg571His	missense_variant	Exon 16 of 18	1	NM_006058.5	ENSP00000430760.1

Frequencies

GnomAD3 genomes AF: 0.0000395 AC: 6 AN: 151898 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000242

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: 0.0000736

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000117 AC: 14 AN: 1193220 Hom.: 0 Cov.: 35 AF XY: 0.00000869 AC XY: 5 AN XY: 575372

African (AFR) AF: 0.00 AC: 0 AN: 25296

American (AMR) AF: 0.00 AC: 0 AN: 18884

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16084

East Asian (EAS) AF: 0.00 AC: 0 AN: 31012

South Asian (SAS) AF: 0.00 AC: 0 AN: 37408

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42550

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4640

European-Non Finnish (NFE) AF: 0.0000144 AC: 14 AN: 969450

Other (OTH) AF: 0.00 AC: 0 AN: 47896

GnomAD4 genome AF: 0.0000395 AC: 6 AN: 151898 Hom.: 0 Cov.: 31 AF XY: 0.0000539 AC XY: 4 AN XY: 74206

African (AFR) AF: 0.0000242 AC: 1 AN: 41342

American (AMR) AF: 0.00 AC: 0 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10576

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000736 AC: 5 AN: 67942

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000264

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 03, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1712G>A (p.R571H) alteration is located in exon 16 (coding exon 15) of the TNIP1 gene. This alteration results from a G to A substitution at nucleotide position 1712, causing the arginine (R) at amino acid position 571 to be replaced by a histidine (H). 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	0.081
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Uncertain	25
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.13	.;.;T;.;T;T;.
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.89	D;D;.;.;.;D;D
M_CAP	Benign	0.017	T
MetaRNN	Uncertain	0.54	D;D;D;D;D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	.;.;M;M;M;M;M
PhyloP100		3.8
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-1.1	N;N;N;N;N;N;N
REVEL	Benign	0.14
Sift	Benign	0.13	T;T;T;T;T;T;T
Sift4G	Benign	0.16	T;T;T;T;T;T;T
Polyphen		1.0	.;.;D;.;D;D;.
Vest4		0.67
MutPred		0.55		.;Loss of catalytic residue at R571 (P = 0.0186);Loss of catalytic residue at R571 (P = 0.0186);Loss of catalytic residue at R571 (P = 0.0186);Loss of catalytic residue at R571 (P = 0.0186);Loss of catalytic residue at R571 (P = 0.0186);Loss of catalytic residue at R571 (P = 0.0186);
MVP		0.17
MPC		0.87
ClinPred		0.95	D
GERP RS		5.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.10
gMVP		0.32
Mutation Taster		=84/16	polymorphism

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

Other links and lift over

dbSNP: rs1168947768; hg19: chr5-150413236;