rs142253225
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_001270508.2(TNFAIP3):c.1939A>C(p.Thr647Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00199 in 1,614,182 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/14 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. T647T) has been classified as Likely benign.
Frequency
Consequence
NM_001270508.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TNFAIP3 | NM_001270508.2 | c.1939A>C | p.Thr647Pro | missense_variant | 8/9 | ENST00000612899.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TNFAIP3 | ENST00000612899.5 | c.1939A>C | p.Thr647Pro | missense_variant | 8/9 | 5 | NM_001270508.2 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00193 AC: 294AN: 152170Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00188 AC: 474AN: 251476Hom.: 0 AF XY: 0.00196 AC XY: 267AN XY: 135912
GnomAD4 exome AF: 0.00200 AC: 2923AN: 1461894Hom.: 2 Cov.: 31 AF XY: 0.00204 AC XY: 1482AN XY: 727248
GnomAD4 genome AF: 0.00193 AC: 294AN: 152288Hom.: 0 Cov.: 33 AF XY: 0.00196 AC XY: 146AN XY: 74468
ClinVar
Submissions by phenotype
not provided Benign:4
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 25, 2024 | - - |
Likely benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jan 01, 2023 | TNFAIP3: BP4, BS1, BS2 - |
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Autoinflammatory syndrome, familial, Behcet-like Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Al Jalila Children’s Genomics Center, Al Jalila Childrens Speciality Hospital | Oct 04, 2020 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Mar 16, 2021 | The TNFAIP3 c.1939A>C; p.Thr647Pro variant (rs142253225) is reported in the literature in one individual with periodic fever and autoinflammatory disease and in a family with symptoms similar to familial Behcet-like autoinflammatory syndrome (Fathalla 2021, Mulhern 2019). This variant is also reported in ClinVar (Variation ID: 135345). Functional analyses of the variant protein in heterologous cells showed reduced expression and lack of significant suppression of the NF-kB signaling pathway (Kadowaki 2021). However, this variant is found in the general population with an allele frequency of 0.18% (511/282864 alleles) in the Genome Aggregation Database. The threonine at codon 647 is weakly conserved, and computational analyses predict that this variant is neutral (REVEL: 0.027). Due to conflicting information, the clinical significance of the p.Thr647Pro variant is uncertain at this time. - |
not specified Other:1
not provided, no classification provided | reference population | ITMI | Sep 19, 2013 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at