Variant 4-2744891-C-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000315423.12(TNIP2):c.712G>T(p.Val238Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000958 in 1,461,046 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000096 ( 0 hom. )

Consequence

TNIP2
ENST00000315423.12 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.31

Variant links:

Genes affected

TNIP2 (HGNC:19118): (TNFAIP3 interacting protein 2) This gene encodes a protein which acts as an inhibitor of NFkappaB activation. The encoded protein is also involved in MAP/ERK signaling pathway in specific cell types. It may be involved in apoptosis of endothelial cells. Alternative splicing results in multiple transcript variants. A pseudogene related to this gene is located on the X chromosome.[provided by RefSeq, May 2014]

TNIP2 links:

TNIP2 (HGNC:):

TNIP2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNIP2	NM_024309.4 linkuse as main transcript	c.712G>T	p.Val238Leu	missense_variant	4/6	ENST00000315423.12	NP_077285.3	Q8NFZ5-1
TNIP2	NM_001161527.2 linkuse as main transcript	c.391G>T	p.Val131Leu	missense_variant	4/6		NP_001154999.1	Q8NFZ5-2
TNIP2	NM_001292016.2 linkuse as main transcript	c.658-385G>T		intron_variant			NP_001278945.1	Q8NFZ5D6RGJ2
TNIP2	XM_047416149.1 linkuse as main transcript	c.337-385G>T		intron_variant			XP_047272105.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNIP2	ENST00000315423.12 linkuse as main transcript	c.712G>T	p.Val238Leu	missense_variant	4/6	1	NM_024309.4	ENSP00000321203.7		Q8NFZ5-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000958

AC:

AN:

1461046

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

726694

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000990

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

Cov.:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 19, 2022

The c.712G>T (p.V238L) alteration is located in exon 4 (coding exon 4) of the TNIP2 gene. This alteration results from a G to T substitution at nucleotide position 712, causing the valine (V) at amino acid position 238 to be replaced by a leucine (L). 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

Uncertain

0.55

BayesDel_addAF

Uncertain

0.054

BayesDel_noAF

Benign

-0.16

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.47

.;T

Eigen

Uncertain

0.55

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.78

T;T

M_CAP

Uncertain

0.099

MetaRNN

Uncertain

0.70

D;D

MetaSVM

Benign

-0.59

MutationAssessor

Uncertain

2.2

.;M

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.65

PROVEAN

Benign

-2.1

N;N

REVEL

Benign

0.16

Sift

Uncertain

0.011

D;D

Sift4G

Uncertain

0.015

D;T

Polyphen

0.99

.;D

Vest4

0.66

MutPred

0.27

.;Gain of glycosylation at Y237 (P = 0.0025);

MVP

0.78

MPC

1.0

ClinPred

0.97

GERP RS

5.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.42

gMVP

0.35

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over