chr15-51058015-T-C
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_001311175.2(TNFAIP8L3):āc.481A>Gā(p.Ile161Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,886 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: not found (cov: 32)
Exomes š: 0.0000021 ( 0 hom. )
Consequence
TNFAIP8L3
NM_001311175.2 missense
NM_001311175.2 missense
Scores
2
5
12
Clinical Significance
Conservation
PhyloP100: 6.20
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.763
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TNFAIP8L3 | NM_001311175.2 | c.481A>G | p.Ile161Val | missense_variant | 2/2 | ENST00000637513.2 | NP_001298104.1 | |
MIR4713HG | NR_146310.1 | n.194+20334T>C | intron_variant, non_coding_transcript_variant | |||||
TNFAIP8L3 | NM_207381.4 | c.745A>G | p.Ile249Val | missense_variant | 3/3 | NP_997264.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TNFAIP8L3 | ENST00000637513.2 | c.481A>G | p.Ile161Val | missense_variant | 2/2 | 1 | NM_001311175.2 | ENSP00000489743 | P1 | |
TNFAIP8L3 | ENST00000327536.5 | c.745A>G | p.Ile249Val | missense_variant | 3/3 | 1 | ENSP00000328016 | |||
MIR4713HG | ENST00000559909.1 | n.194+20334T>C | intron_variant, non_coding_transcript_variant | 4 | ||||||
TNFAIP8L3 | ENST00000649177.1 | c.343A>G | p.Ile115Val | missense_variant | 2/2 | ENSP00000498365 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251358Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135846
GnomAD3 exomes
AF:
AC:
1
AN:
251358
Hom.:
AF XY:
AC XY:
0
AN XY:
135846
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461886Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2AN XY: 727242
GnomAD4 exome
AF:
AC:
3
AN:
1461886
Hom.:
Cov.:
31
AF XY:
AC XY:
2
AN XY:
727242
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
Bravo
AF:
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 | Nov 17, 2022 | The c.745A>G (p.I249V) alteration is located in exon 3 (coding exon 3) of the TNFAIP8L3 gene. This alteration results from a A to G substitution at nucleotide position 745, causing the isoleucine (I) at amino acid position 249 to be replaced by a valine (V). 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
Uncertain
DEOGEN2
Benign
T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
T
MetaRNN
Pathogenic
D;D
MetaSVM
Benign
T
MutationAssessor
Benign
L;.
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;.
REVEL
Benign
Sift
Benign
T;.
Sift4G
Benign
T;.
Polyphen
D;.
Vest4
MutPred
Gain of methylation at R248 (P = 0.0519);.;
MVP
MPC
ClinPred
D
GERP RS
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