5-151033786-C-G

Variant names:

• chr5-151033786-C-G
• rs753833491
• NM_006058.5:c.1601G>C

Variant summary

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

The NM_006058.5(TNIP1):​c.1601G>C​(p.Arg534Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000164 in 1,217,760 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: not found (cov: 31)
  • Exomes 𝑓: 0.0000016 (0 hom.)
• Consequence: TNIP1 NM_006058.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.57
• Publications: 0 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 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	c.1601G>C	p.Arg534Pro	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.1601G>C	p.Arg534Pro	missense_variant	Exon 16 of 18	1	NM_006058.5	ENSP00000430760.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000164 AC: 2 AN: 1217760 Hom.: 0 Cov.: 36 AF XY: 0.00000170 AC XY: 1 AN XY: 587558

African (AFR) AF: 0.00 AC: 0 AN: 25508

American (AMR) AF: 0.00 AC: 0 AN: 18900

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16692

East Asian (EAS) AF: 0.00 AC: 0 AN: 31050

South Asian (SAS) AF: 0.0000502 AC: 2 AN: 39878

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44124

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4754

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 987548

Other (OTH) AF: 0.00 AC: 0 AN: 49306

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.40
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.27	.;.;T;.;T;T;.
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.91	D;D;.;.;.;D;D
M_CAP	Benign	0.018	T
MetaRNN	Uncertain	0.59	D;D;D;D;D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	.;.;M;M;M;M;M
PhyloP100		2.6
PrimateAI	Uncertain	0.54	T
PROVEAN	Uncertain	-2.4	N;N;N;N;N;N;N
REVEL	Benign	0.27
Sift	Uncertain	0.014	D;D;D;D;D;D;D
Sift4G	Uncertain	0.013	D;D;D;D;D;D;D
Polyphen		1.0	.;.;D;.;D;D;.
Vest4		0.81
MutPred		0.49		.;Loss of MoRF binding (P = 0.0183);Loss of MoRF binding (P = 0.0183);Loss of MoRF binding (P = 0.0183);Loss of MoRF binding (P = 0.0183);Loss of MoRF binding (P = 0.0183);Loss of MoRF binding (P = 0.0183);
MVP		0.25
MPC		0.84
ClinPred		0.97	D
GERP RS		5.3
Varity_R		0.73
gMVP		0.69
Mutation Taster		=56/44	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs753833491; hg19: chr5-150413347;