NM_001311175.2:c.603G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001311175.2(TNFAIP8L3):​c.603G>C​(p.Glu201Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000368 in 1,576,586 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 0.000039 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000037 ( 0 hom. )

Consequence

TNFAIP8L3
NM_001311175.2 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.17

Publications

0 publications found
Variant links:
Genes affected
TNFAIP8L3 (HGNC:20620): (TNF alpha induced protein 8 like 3) Predicted to enable phosphatidylinositol binding activity and phosphatidylinositol transfer activity. Predicted to be involved in several processes, including inositol lipid-mediated signaling; positive regulation of intracellular signal transduction; and positive regulation of phosphatidylinositol 3-kinase activity. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]
MIR4713HG (HGNC:53124): (MIR4713 host gene)

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.17575324).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TNFAIP8L3NM_001311175.2 linkc.603G>C p.Glu201Asp missense_variant Exon 2 of 2 ENST00000637513.2 NP_001298104.1 Q5GJ75A0A1B0GTK8
TNFAIP8L3NM_207381.4 linkc.867G>C p.Glu289Asp missense_variant Exon 3 of 3 NP_997264.2 Q5GJ75
MIR4713HGNR_146310.1 linkn.194+20212C>G intron_variant Intron 1 of 2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TNFAIP8L3ENST00000637513.2 linkc.603G>C p.Glu201Asp missense_variant Exon 2 of 2 1 NM_001311175.2 ENSP00000489743.1 A0A1B0GTK8

Frequencies

GnomAD3 genomes
AF:
0.0000394
AC:
6
AN:
152230
Hom.:
0
Cov.:
32
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:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000882
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.0000358
AC:
8
AN:
223204
AF XY:
0.0000418
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000771
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000365
AC:
52
AN:
1424356
Hom.:
0
Cov.:
30
AF XY:
0.0000383
AC XY:
27
AN XY:
704438
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
32260
American (AMR)
AF:
0.00
AC:
0
AN:
39200
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
23788
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39310
South Asian (SAS)
AF:
0.00
AC:
0
AN:
79412
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
52352
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5562
European-Non Finnish (NFE)
AF:
0.0000475
AC:
52
AN:
1093678
Other (OTH)
AF:
0.00
AC:
0
AN:
58794
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.470
Heterozygous variant carriers
0
4
7
11
14
18
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:
0.0000394
AC:
6
AN:
152230
Hom.:
0
Cov.:
32
AF XY:
0.0000134
AC XY:
1
AN XY:
74364
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
41464
American (AMR)
AF:
0.00
AC:
0
AN:
15290
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3472
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5200
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4826
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10620
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
0.0000882
AC:
6
AN:
68036
Other (OTH)
AF:
0.00
AC:
0
AN:
2094
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
1
2
2
3
4
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:
0.0000488
Hom.:
0
Bravo
AF:
0.0000302
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000330
AC:
4

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Mar 16, 2025
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.867G>C (p.E289D) alteration is located in exon 3 (coding exon 3) of the TNFAIP8L3 gene. This alteration results from a G to C substitution at nucleotide position 867, causing the glutamic acid (E) at amino acid position 289 to be replaced by an aspartic acid (D). 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
0.19
BayesDel_addAF
Benign
-0.33
T
BayesDel_noAF
Benign
-0.52
CADD
Benign
15
DANN
Uncertain
0.99
DEOGEN2
Benign
0.091
T;.
Eigen
Benign
-0.31
Eigen_PC
Benign
-0.19
FATHMM_MKL
Uncertain
0.87
D
LIST_S2
Benign
0.76
T;T
M_CAP
Benign
0.0049
T
MetaRNN
Benign
0.18
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.9
L;.
PhyloP100
1.2
PrimateAI
Uncertain
0.53
T
PROVEAN
Benign
-1.9
N;.
REVEL
Benign
0.070
Sift
Benign
0.12
T;.
Sift4G
Benign
0.21
T;.
Polyphen
0.0050
B;.
Vest4
0.17
MutPred
0.73
Loss of ubiquitination at K285 (P = 0.0949);.;
MVP
0.14
MPC
0.20
ClinPred
0.059
T
GERP RS
1.1
Varity_R
0.27
gMVP
0.38
Mutation Taster
=81/19
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: rs200888133; hg19: chr15-51350090; API