5-151033760-G-A
Variant names:
Variant summary
Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4
The NM_006058.5(TNIP1):c.1627C>T(p.His543Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.0000107 in 1,212,690 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 0.0000066 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000011 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
TNIP1
NM_006058.5 missense
NM_006058.5 missense
Scores
7
12
Clinical Significance
Conservation
PhyloP100: 3.80
Publications
0 publications found
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]
TNIP1 Gene-Disease associations (from GenCC):
- systemic lupus erythematosusInheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.28605902).
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes 0.00000657 AC: 1AN: 152188Hom.: 0 Cov.: 31 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
152188
Hom.:
Cov.:
31
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 0.0000107 AC: 13AN: 1212690Hom.: 0 Cov.: 36 AF XY: 0.0000120 AC XY: 7AN XY: 584946 show subpopulations
GnomAD4 exome
AF:
AC:
13
AN:
1212690
Hom.:
Cov.:
36
AF XY:
AC XY:
7
AN XY:
584946
show subpopulations
African (AFR)
AF:
AC:
0
AN:
25484
American (AMR)
AF:
AC:
0
AN:
18848
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
16584
East Asian (EAS)
AF:
AC:
0
AN:
31022
South Asian (SAS)
AF:
AC:
0
AN:
39386
European-Finnish (FIN)
AF:
AC:
0
AN:
43860
Middle Eastern (MID)
AF:
AC:
0
AN:
4772
European-Non Finnish (NFE)
AF:
AC:
13
AN:
983724
Other (OTH)
AF:
AC:
0
AN:
49010
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.483
Heterozygous variant carriers
0
1
2
3
4
5
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome 0.00000657 AC: 1AN: 152188Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1AN XY: 74342 show subpopulations ⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.
GnomAD4 genome
Data not reliable, filtered out with message: AS_VQSR
AF:
AC:
1
AN:
152188
Hom.:
Cov.:
31
AF XY:
AC XY:
1
AN XY:
74342
show subpopulations
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
1
AN:
41444
American (AMR)
AF:
AC:
0
AN:
15288
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3472
East Asian (EAS)
AF:
AC:
0
AN:
5194
South Asian (SAS)
AF:
AC:
0
AN:
4832
European-Finnish (FIN)
AF:
AC:
0
AN:
10620
Middle Eastern (MID)
AF:
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
AC:
0
AN:
68024
Other (OTH)
AF:
AC:
0
AN:
2088
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.275
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Apr 28, 2025
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing
The c.1627C>T (p.H543Y) alteration is located in exon 16 (coding exon 15) of the TNIP1 gene. This alteration results from a C to T substitution at nucleotide position 1627, causing the histidine (H) at amino acid position 543 to be replaced by a tyrosine (Y). 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
DANN
Uncertain
DEOGEN2
Benign
.;.;T;.;T;T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;.;.;.;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
.;.;M;M;M;M;M
PhyloP100
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;N;N;N;N
REVEL
Benign
Sift
Benign
T;T;T;D;T;T;D
Sift4G
Benign
T;T;T;T;T;T;T
Polyphen
0.99
.;.;D;.;D;D;.
Vest4
MutPred
0.60
.;Gain of phosphorylation at H543 (P = 0.0164);Gain of phosphorylation at H543 (P = 0.0164);Gain of phosphorylation at H543 (P = 0.0164);Gain of phosphorylation at H543 (P = 0.0164);Gain of phosphorylation at H543 (P = 0.0164);Gain of phosphorylation at H543 (P = 0.0164);
MVP
MPC
0.86
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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