4-2744738-G-A
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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
ENST00000315423.12 missense
Scores
1
8
10
Clinical Significance
Conservation
PhyloP100: 0.778
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]
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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 |
---|---|---|---|---|---|---|---|---|
TNIP2 | NM_024309.4 | c.865C>T | p.Arg289Trp | missense_variant | 4/6 | ENST00000315423.12 | NP_077285.3 | |
TNIP2 | NM_001161527.2 | c.544C>T | p.Arg182Trp | missense_variant | 4/6 | NP_001154999.1 | ||
TNIP2 | NM_001292016.2 | c.658-232C>T | intron_variant | NP_001278945.1 | ||||
TNIP2 | XM_047416149.1 | c.337-232C>T | intron_variant | XP_047272105.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TNIP2 | ENST00000315423.12 | c.865C>T | p.Arg289Trp | missense_variant | 4/6 | 1 | NM_024309.4 | ENSP00000321203.7 |
Frequencies
GnomAD3 genomes AF: 0.0000657 AC: 10AN: 152230Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000528 AC: 13AN: 246376Hom.: 0 AF XY: 0.0000598 AC XY: 8AN XY: 133724
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GnomAD4 exome AF: 0.000103 AC: 150AN: 1454640Hom.: 0 Cov.: 34 AF XY: 0.000128 AC XY: 93AN XY: 724018
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GnomAD4 genome AF: 0.0000657 AC: 10AN: 152230Hom.: 0 Cov.: 33 AF XY: 0.0000941 AC XY: 7AN XY: 74366
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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 | May 01, 2022 | The 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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Uncertain
.;D
Eigen
Uncertain
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Uncertain
D;D
M_CAP
Uncertain
D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
.;M
MutationTaster
Benign
N;N;N
PrimateAI
Benign
T
PROVEAN
Pathogenic
D;D
REVEL
Benign
Sift
Uncertain
D;D
Sift4G
Uncertain
D;D
Polyphen
1.0
.;D
Vest4
MutPred
0.52
.;Gain of glycosylation at T287 (P = 0.0019);
MVP
MPC
0.36
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at