15-51058286-G-C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001311175.2(TNFAIP8L3):​c.210C>G​(p.Asn70Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000329 in 152,114 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Consequence

TNFAIP8L3
NM_001311175.2 missense

Scores

4
7
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.04

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 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TNFAIP8L3NM_001311175.2 linkc.210C>G p.Asn70Lys missense_variant Exon 2 of 2 ENST00000637513.2 NP_001298104.1 Q5GJ75A0A1B0GTK8
TNFAIP8L3NM_207381.4 linkc.474C>G p.Asn158Lys missense_variant Exon 3 of 3 NP_997264.2 Q5GJ75
MIR4713HGNR_146310.1 linkn.194+20605G>C intron_variant Intron 1 of 2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TNFAIP8L3ENST00000637513.2 linkc.210C>G p.Asn70Lys missense_variant Exon 2 of 2 1 NM_001311175.2 ENSP00000489743.1 A0A1B0GTK8

Frequencies

GnomAD3 genomes
AF:
0.0000329
AC:
5
AN:
152114
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000242
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000262
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
Cov.:
31
GnomAD4 genome
AF:
0.0000329
AC:
5
AN:
152114
Hom.:
0
Cov.:
32
AF XY:
0.0000404
AC XY:
3
AN XY:
74306
show subpopulations
African (AFR)
AF:
0.0000242
AC:
1
AN:
41400
American (AMR)
AF:
0.000262
AC:
4
AN:
15276
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3470
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5194
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4822
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10606
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
68024
Other (OTH)
AF:
0.00
AC:
0
AN:
2094
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
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:
0.00
Hom.:
0
Bravo
AF:
0.000110

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Feb 01, 2025
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.474C>G (p.N158K) alteration is located in exon 3 (coding exon 3) of the TNFAIP8L3 gene. This alteration results from a C to G substitution at nucleotide position 474, causing the asparagine (N) at amino acid position 158 to be replaced by a lysine (K). 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
Pathogenic
0.68
BayesDel_addAF
Benign
-0.10
T
BayesDel_noAF
Benign
-0.39
CADD
Uncertain
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.31
T;.
Eigen
Uncertain
0.62
Eigen_PC
Pathogenic
0.66
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.95
D;D
M_CAP
Benign
0.011
T
MetaRNN
Uncertain
0.52
D;D
MetaSVM
Benign
-0.85
T
MutationAssessor
Uncertain
2.8
M;.
PhyloP100
8.0
PrimateAI
Benign
0.47
T
PROVEAN
Pathogenic
-4.4
D;.
REVEL
Benign
0.25
Sift
Uncertain
0.0040
D;.
Sift4G
Uncertain
0.0060
D;.
Polyphen
0.90
P;.
Vest4
0.41
MutPred
0.63
Gain of methylation at N158 (P = 0.0142);.;
MVP
0.45
MPC
0.63
ClinPred
0.98
D
GERP RS
5.5
Varity_R
0.61
gMVP
0.41

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: rs892611225; hg19: chr15-51350483; API