Variant 4-121216430-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001244764.2(TNIP3):c.74C>T(p.Ser25Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000326 in 1,535,326 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000029 ( 0 hom. )

Consequence

TNIP3
NM_001244764.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.24

Variant links:

Genes affected

TNIP3 (HGNC:19315): (TNFAIP3 interacting protein 3) Enables polyubiquitin modification-dependent protein binding activity. Involved in cellular response to lipopolysaccharide; negative regulation of I-kappaB kinase/NF-kappaB signaling; and toll-like receptor signaling pathway. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

TNIP3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.047333837).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	Protein	UniProt
TNIP3	NM_001244764.2 linkuse as main transcript	c.74C>T	p.Ser25Phe	missense_variant	2/13	NP_001231693.1	Q96KP6-3
TNIP3	NM_001128843.2 linkuse as main transcript	c.53C>T	p.Ser18Phe	missense_variant	2/13	NP_001122315.2	Q96KP6-2
TNIP3	XM_011532256.3 linkuse as main transcript	c.74C>T	p.Ser25Phe	missense_variant	2/15	XP_011530558.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNIP3	ENST00000509841.1 linkuse as main transcript	c.74C>T	p.Ser25Phe	missense_variant	2/13	2		ENSP00000426613.1		Q96KP6-3
TNIP3	ENST00000507879.5 linkuse as main transcript	c.53C>T	p.Ser18Phe	missense_variant	2/13	2		ENSP00000427106.1		Q96KP6-2

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152088

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000289

AC:

AN:

1383238

Hom.:

Cov.:

AF XY:

0.00000293

AC XY:

AN XY:

682582

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000112

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000658

AC:

AN:

152088

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74294

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

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

Oct 12, 2021

The c.53C>T (p.S18F) alteration is located in exon 2 (coding exon 1) of the TNIP3 gene. This alteration results from a C to T substitution at nucleotide position 53, causing the serine (S) at amino acid position 18 to be replaced by a phenylalanine (F). 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

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.63

CADD

Benign

5.2

DANN

Uncertain

0.99

Eigen

Benign

-0.86

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.014

LIST_S2

Benign

0.49

T;T

M_CAP

Benign

0.021

MetaRNN

Benign

0.047

T;T

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.42

N;N

REVEL

Benign

0.046

Sift

Uncertain

0.022

D;D

Sift4G

Benign

0.16

T;T

Vest4

0.094

MutPred

0.18

.;Gain of glycosylation at S28 (P = 0.01);

MVP

0.11

MPC

0.28

ClinPred

0.14

GERP RS

-2.6

gMVP

0.059

Splicing

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