4-2744738-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The ENST00000315423.12(TNIP2):​c.865C>T​(p.Arg289Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000996 in 1,606,870 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00010 ( 0 hom. )

Consequence

TNIP2
ENST00000315423.12 missense

Scores

1
8
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.778
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.3164966).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TNIP2NM_024309.4 linkuse as main transcriptc.865C>T p.Arg289Trp missense_variant 4/6 ENST00000315423.12 NP_077285.3 Q8NFZ5-1
TNIP2NM_001161527.2 linkuse as main transcriptc.544C>T p.Arg182Trp missense_variant 4/6 NP_001154999.1 Q8NFZ5-2
TNIP2NM_001292016.2 linkuse as main transcriptc.658-232C>T intron_variant NP_001278945.1 Q8NFZ5D6RGJ2
TNIP2XM_047416149.1 linkuse as main transcriptc.337-232C>T intron_variant XP_047272105.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TNIP2ENST00000315423.12 linkuse as main transcriptc.865C>T p.Arg289Trp missense_variant 4/61 NM_024309.4 ENSP00000321203.7 Q8NFZ5-1

Frequencies

GnomAD3 genomes
AF:
0.0000657
AC:
10
AN:
152230
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000262
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:
0.0000735
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.0000528
AC:
13
AN:
246376
Hom.:
0
AF XY:
0.0000598
AC XY:
8
AN XY:
133724
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000868
Gnomad ASJ exome
AF:
0.0000994
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000617
Gnomad OTH exome
AF:
0.000329
GnomAD4 exome
AF:
0.000103
AC:
150
AN:
1454640
Hom.:
0
Cov.:
34
AF XY:
0.000128
AC XY:
93
AN XY:
724018
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000134
Gnomad4 ASJ exome
AF:
0.000191
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000112
Gnomad4 OTH exome
AF:
0.000166
GnomAD4 genome
AF:
0.0000657
AC:
10
AN:
152230
Hom.:
0
Cov.:
33
AF XY:
0.0000941
AC XY:
7
AN XY:
74366
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000262
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000735
Gnomad4 OTH
AF:
0.000478
Alfa
AF:
0.0000274
Hom.:
0
Bravo
AF:
0.0000567
ExAC
AF:
0.0000659
AC:
8
EpiCase
AF:
0.000109
EpiControl
AF:
0.000119

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 submitterclinical testingAmbry GeneticsMay 01, 2022The c.865C>T (p.R289W) alteration is located in exon 4 (coding exon 4) of the TNIP2 gene. This alteration results from a C to T substitution at nucleotide position 865, causing the arginine (R) at amino acid position 289 to be replaced by a tryptophan (W). 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
0.12
BayesDel_addAF
Benign
-0.19
T
BayesDel_noAF
Benign
-0.31
CADD
Benign
23
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.65
.;D
Eigen
Uncertain
0.21
Eigen_PC
Benign
0.064
FATHMM_MKL
Benign
0.29
N
LIST_S2
Uncertain
0.87
D;D
M_CAP
Uncertain
0.10
D
MetaRNN
Benign
0.32
T;T
MetaSVM
Benign
-0.78
T
MutationAssessor
Uncertain
2.4
.;M
MutationTaster
Benign
1.0
N;N;N
PrimateAI
Benign
0.38
T
PROVEAN
Pathogenic
-4.8
D;D
REVEL
Benign
0.15
Sift
Uncertain
0.0010
D;D
Sift4G
Uncertain
0.0050
D;D
Polyphen
1.0
.;D
Vest4
0.18
MutPred
0.52
.;Gain of glycosylation at T287 (P = 0.0019);
MVP
0.87
MPC
0.36
ClinPred
0.38
T
GERP RS
4.4
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.61
gMVP
0.48

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.

Other links and lift over

dbSNP: rs745310133; hg19: chr4-2746465; API