Variant chr4-2744419-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_024309.4(TNIP2):c.994G>A(p.Ala332Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000871 in 1,614,240 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00043 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00092 ( 0 hom. )

Consequence

TNIP2
NM_024309.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0260

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.017576247).

BP6

Variant 4-2744419-C-T is Benign according to our data. Variant chr4-2744419-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2320177.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
TNIP2	NM_024309.4 linkuse as main transcript	c.994G>A	p.Ala332Thr	missense_variant	5/6	ENST00000315423.12
TNIP2	NM_001292016.2 linkuse as main transcript	c.745G>A	p.Ala249Thr	missense_variant	4/5
TNIP2	NM_001161527.2 linkuse as main transcript	c.673G>A	p.Ala225Thr	missense_variant	5/6
TNIP2	XM_047416149.1 linkuse as main transcript	c.424G>A	p.Ala142Thr	missense_variant	4/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNIP2	ENST00000315423.12 linkuse as main transcript	c.994G>A	p.Ala332Thr	missense_variant	5/6	1	NM_024309.4	P1	Q8NFZ5-1

Frequencies

GnomAD3 genomes

AF:

0.000434

AC:

AN:

152240

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000764

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000461

AC:

116

AN:

251490

Hom.:

AF XY:

0.000493

AC XY:

AN XY:

135920

show subpopulations

Gnomad AFR exome

AF:

0.000369

Gnomad AMR exome

AF:

0.000434

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.000791

Gnomad OTH exome

AF:

0.000651

GnomAD4 exome

AF:

0.000917

AC:

1340

AN:

1461882

Hom.:

Cov.:

AF XY:

0.000868

AC XY:

631

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.000299

Gnomad4 AMR exome

AF:

0.000581

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000374

Gnomad4 NFE exome

AF:

0.00113

Gnomad4 OTH exome

AF:

0.000662

GnomAD4 genome

AF:

0.000433

AC:

AN:

152358

Hom.:

Cov.:

AF XY:

0.000376

AC XY:

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.000240

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.000764

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000765

Hom.:

Bravo

AF:

0.000597

TwinsUK

AF:

0.00162

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000814

AC:

ExAC

AF:

0.000338

AC:

EpiCase

AF:

0.00109

EpiControl

AF:

0.000593

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

May 09, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.75

CADD

Benign

3.4

DANN

Benign

0.75

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.21

LIST_S2

Benign

0.13

T;T;T

M_CAP

Benign

0.0085

MetaRNN

Benign

0.018

T;T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.79

N;N;N

REVEL

Benign

0.024

Sift

Benign

0.37

T;T;T

Sift4G

Benign

0.21

T;T;T

Polyphen

0.021, 0.41

.;B;B

Vest4

0.10

MVP

0.38

MPC

0.31

ClinPred

0.0020

GERP RS

0.14

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.092

gMVP

0.11

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over