rs5029941
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_001270508.2(TNFAIP3):c.374C>T(p.Ala125Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000935 in 1,614,222 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
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.374C>T | p.Ala125Val | missense_variant | 3/9 | ENST00000612899.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TNFAIP3 | ENST00000612899.5 | c.374C>T | p.Ala125Val | missense_variant | 3/9 | 5 | NM_001270508.2 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00528 AC: 804AN: 152212Hom.: 8 Cov.: 33
GnomAD3 exomes AF: 0.00120 AC: 303AN: 251472Hom.: 3 AF XY: 0.000876 AC XY: 119AN XY: 135906
GnomAD4 exome AF: 0.000482 AC: 704AN: 1461892Hom.: 7 Cov.: 33 AF XY: 0.000430 AC XY: 313AN XY: 727246
GnomAD4 genome ? AF: 0.00528 AC: 805AN: 152330Hom.: 8 Cov.: 33 AF XY: 0.00510 AC XY: 380AN XY: 74488
ClinVar
Submissions by phenotype
not specified Uncertain:1Other:1
not provided, no classification provided | reference population | ITMI | Sep 19, 2013 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia | Oct 13, 2015 | - - |
Autoinflammatory syndrome, familial, Behcet-like Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Sep 18, 2021 | The TNFAIP3 c.374C>T; p.Ala125Val variant (rs5029941), to our knowledge, has not been reported in individuals with Behcet-like autoinflammatory syndrome but has been reported to mediate risk for other inflammatory related disorders (Lodolce 2010). Functional analyses of the variant protein show diminished deubiquitination and degradation activity, although it is unclear whether this results in increased or decreased inflammation (Lodolce 2010). This variant is also reported in ClinVar (Variation ID: 135332). This variant is found in the African population with an allele frequency of 1.7% (434/24970 alleles, including 4 homozygotes) in the Genome Aggregation Database. The alanine at codon 125 is moderately conserved, but computational analyses predict that this variant is neutral (REVEL: 0.078). Although the population frequency of this variant is relatively high, the possibility of reduced penetrance or a mild effect cannot be excluded. Therefore, due to a lack of clinical and functional data, the significance of this variant cannot be determined with certainty. Reference Lodolce JP et al. African-derived genetic polymorphisms in TNFAIP3 mediate risk for autoimmunity. J Immunol. 2010 Jun 15;184(12):7001-9. PMID: 20483768. - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 26, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at