5-151036890-G-A
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The ENST00000521591.6(TNIP1):c.1295C>T(p.Pro432Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000236 in 1,612,026 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 Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000092 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000016 ( 0 hom. )
Consequence
TNIP1
ENST00000521591.6 missense
ENST00000521591.6 missense
Scores
1
2
16
Clinical Significance
Conservation
PhyloP100: 6.76
Genes affected
TNIP1 (HGNC:16903): (TNFAIP3 interacting protein 1) This gene encodes an A20-binding protein which plays a role in autoimmunity and tissue homeostasis through the regulation of nuclear factor kappa-B activation. Mutations in this gene have been associated with psoriatic arthritis, rheumatoid arthritis, and systemic lupus erythematosus. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2011]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.13025394).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TNIP1 | NM_006058.5 | c.1295C>T | p.Pro432Leu | missense_variant | 13/18 | ENST00000521591.6 | NP_006049.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TNIP1 | ENST00000521591.6 | c.1295C>T | p.Pro432Leu | missense_variant | 13/18 | 1 | NM_006058.5 | ENSP00000430760 | P3 |
Frequencies
GnomAD3 genomes AF: 0.0000920 AC: 14AN: 152178Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000161 AC: 4AN: 248832Hom.: 0 AF XY: 0.0000149 AC XY: 2AN XY: 134618
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GnomAD4 exome AF: 0.0000164 AC: 24AN: 1459848Hom.: 0 Cov.: 30 AF XY: 0.0000193 AC XY: 14AN XY: 726256
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GnomAD4 genome AF: 0.0000920 AC: 14AN: 152178Hom.: 0 Cov.: 32 AF XY: 0.0000942 AC XY: 7AN XY: 74344
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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 | Jan 27, 2022 | The c.1295C>T (p.P432L) alteration is located in exon 13 (coding exon 12) of the TNIP1 gene. This alteration results from a C to T substitution at nucleotide position 1295, causing the proline (P) at amino acid position 432 to be replaced by a leucine (L). 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
Benign
DEOGEN2
Benign
.;.;.;.;T;.;.;T;T;.;.;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D;D;.;.;.;.;D;D;.;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
.;.;N;.;N;N;N;N;N;N;N;N
MutationTaster
Benign
D;D;D;D;D;D;D;D;D
PrimateAI
Benign
T
PROVEAN
Benign
N;N;.;N;N;N;.;N;N;N;N;N
REVEL
Benign
Sift
Uncertain
D;T;.;T;T;T;.;T;T;T;T;T
Sift4G
Benign
T;T;T;T;T;T;T;T;T;T;T;T
Polyphen
0.35
.;.;.;.;B;.;.;B;B;.;.;.
Vest4
MVP
MPC
0.25
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