5-151049846-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006058.5(TNIP1):c.824A>C(p.Lys275Thr) 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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TNIP1 NM_006058.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.27

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13662899).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNIP1	NM_006058.5	c.824A>C	p.Lys275Thr	missense_variant	8/18	ENST00000521591.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNIP1	ENST00000521591.6	c.824A>C	p.Lys275Thr	missense_variant	8/18	1	NM_006058.5	P3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 04, 2022

The c.824A>C (p.K275T) alteration is located in exon 8 (coding exon 7) of the TNIP1 gene. This alteration results from a A to C substitution at nucleotide position 824, causing the lysine (K) at amino acid position 275 to be replaced by a threonine (T). 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	0.086
BayesDel_addAF	Benign	-0.095	T
BayesDel_noAF	Benign	-0.37
Cadd	Benign	19
Dann	Uncertain	1.0
Eigen	Benign	-0.048
Eigen_PC	Benign	0.053
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.89	D;D;D;.;.;.;.;D;D;.;D;D
M_CAP	Benign	0.0093	T
MetaRNN	Benign	0.14	T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	0.69	D;D;D;D;D;D;D;D;D
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-1.1	N;N;.;N;N;.;N;N;N;N;N;D
REVEL	Benign	0.13
Sift	Uncertain	0.020	D;T;.;T;T;.;T;T;T;T;T;D
Sift4G	Benign	0.15	T;T;T;T;T;T;T;T;T;T;T;.
Polyphen		0.035	.;.;.;B;.;.;B;B;.;.;.;.
Vest4		0.30
MutPred		0.17		.;Loss of ubiquitination at K275 (P = 0.0056);Loss of ubiquitination at K275 (P = 0.0056);Loss of ubiquitination at K275 (P = 0.0056);Loss of ubiquitination at K275 (P = 0.0056);Loss of ubiquitination at K275 (P = 0.0056);Loss of ubiquitination at K275 (P = 0.0056);Loss of ubiquitination at K275 (P = 0.0056);Loss of ubiquitination at K275 (P = 0.0056);Loss of ubiquitination at K275 (P = 0.0056);Loss of ubiquitination at K275 (P = 0.0056);.;
MVP		0.16
MPC		0.89
ClinPred		0.87	D
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.091
gMVP		0.27

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-150429407;