rs752544824

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_006058.5(TNIP1):​c.1698C>G​(p.Asp566Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000111 in 1,352,810 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

TNIP1
NM_006058.5 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0910

Publications

0 publications found
Variant links:
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 erythematosus
    Inheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.031190395).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TNIP1NM_006058.5 linkc.1698C>G p.Asp566Glu missense_variant Exon 16 of 18 ENST00000521591.6 NP_006049.3 Q15025-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TNIP1ENST00000521591.6 linkc.1698C>G p.Asp566Glu missense_variant Exon 16 of 18 1 NM_006058.5 ENSP00000430760.1 Q15025-1

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152090
Hom.:
0
Cov.:
31
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:
0.000578
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.0000717
AC:
9
AN:
125450
AF XY:
0.0000594
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00109
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000999
AC:
12
AN:
1200720
Hom.:
0
Cov.:
35
AF XY:
0.00000863
AC XY:
5
AN XY:
579436
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
25394
American (AMR)
AF:
0.00
AC:
0
AN:
19032
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
16198
East Asian (EAS)
AF:
0.000354
AC:
11
AN:
31050
South Asian (SAS)
AF:
0.00
AC:
0
AN:
38914
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
43190
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
4712
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
973992
Other (OTH)
AF:
0.0000207
AC:
1
AN:
48238
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.496
Heterozygous variant carriers
0
1
2
4
5
6
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152090
Hom.:
0
Cov.:
31
AF XY:
0.0000135
AC XY:
1
AN XY:
74300
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
41404
American (AMR)
AF:
0.00
AC:
0
AN:
15280
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3470
East Asian (EAS)
AF:
0.000578
AC:
3
AN:
5186
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4830
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10614
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
67990
Other (OTH)
AF:
0.00
AC:
0
AN:
2088
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.508
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.00
Hom.:
0
Bravo
AF:
0.0000567
ExAC
AF:
0.0000862
AC:
10

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Mar 29, 2024
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.1698C>G (p.D566E) alteration is located in exon 16 (coding exon 15) of the TNIP1 gene. This alteration results from a C to G substitution at nucleotide position 1698, causing the aspartic acid (D) at amino acid position 566 to be replaced by a glutamic acid (E). 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
0.15
BayesDel_addAF
Benign
-0.55
T
BayesDel_noAF
Benign
-0.62
CADD
Benign
15
DANN
Uncertain
0.99
DEOGEN2
Benign
0.11
.;.;T;.;T;T;.
Eigen
Benign
-0.24
Eigen_PC
Benign
-0.11
FATHMM_MKL
Benign
0.71
D
LIST_S2
Benign
0.74
T;T;.;.;.;T;T
M_CAP
Benign
0.0069
T
MetaRNN
Benign
0.031
T;T;T;T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.3
.;.;L;L;L;L;L
PhyloP100
0.091
PrimateAI
Uncertain
0.58
T
PROVEAN
Benign
-0.62
N;N;N;N;N;N;N
REVEL
Benign
0.041
Sift
Benign
0.16
T;T;T;T;T;T;T
Sift4G
Benign
0.18
T;T;T;T;T;T;T
Polyphen
0.0060
.;.;B;.;B;B;.
Vest4
0.22
MutPred
0.30
.;Gain of loop (P = 0.1081);Gain of loop (P = 0.1081);Gain of loop (P = 0.1081);Gain of loop (P = 0.1081);Gain of loop (P = 0.1081);Gain of loop (P = 0.1081);
MVP
0.068
MPC
0.20
ClinPred
0.050
T
GERP RS
3.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.038
gMVP
0.43
Mutation Taster
=93/7
polymorphism

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

Other links and lift over

dbSNP: rs752544824; hg19: chr5-150413250; API