rs141920055
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Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 1P and 9B. PP2BP4_StrongBP6BS2
The NM_145725.3(TRAF3):c.449G>A(p.Arg150His) variant causes a missense change. The variant allele was found at a frequency of 0.000416 in 1,614,152 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.00078 ( 1 hom., cov: 33)
Exomes 𝑓: 0.00038 ( 3 hom. )
Consequence
TRAF3
NM_145725.3 missense
NM_145725.3 missense
Scores
2
1
14
Clinical Significance
Conservation
PhyloP100: 5.39
Genes affected
TRAF3 (HGNC:12033): (TNF receptor associated factor 3) The protein encoded by this gene is a member of the TNF receptor associated factor (TRAF) protein family. TRAF proteins associate with, and mediate the signal transduction from, members of the TNF receptor (TNFR) superfamily. This protein participates in the signal transduction of CD40, a TNFR family member important for the activation of the immune response. This protein is found to be a critical component of the lymphotoxin-beta receptor (LTbetaR) signaling complex, which induces NF-kappaB activation and cell death initiated by LTbeta ligation. Epstein-Barr virus encoded latent infection membrane protein-1 (LMP1) can interact with this and several other members of the TRAF family, which may be essential for the oncogenic effects of LMP1. The protein also plays a role in the regulation of antiviral response. Mutations in this are associated with Encephalopathy, acute, infection-induced, herpes-specific 5. [provided by RefSeq, Jul 2020]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -8 ACMG points.
PP2
?
Missense variant where missense usually causes diseases, TRAF3
BP4
?
Computational evidence support a benign effect (MetaRNN=0.005728811).
BP6
?
Variant 14-102876404-G-A is Benign according to our data. Variant chr14-102876404-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 252788.We mark this variant Likely_benign, oryginal submissions are: {Benign=2, Uncertain_significance=1}.
BS2
?
High AC in GnomAd4 at 119 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TRAF3 | NM_145725.3 | c.449G>A | p.Arg150His | missense_variant | 6/12 | ENST00000392745.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TRAF3 | ENST00000392745.8 | c.449G>A | p.Arg150His | missense_variant | 6/12 | 1 | NM_145725.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000782 AC: 119AN: 152160Hom.: 1 Cov.: 33
GnomAD3 genomes
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GnomAD3 exomes AF: 0.000704 AC: 177AN: 251470Hom.: 1 AF XY: 0.000692 AC XY: 94AN XY: 135918
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GnomAD4 exome AF: 0.000378 AC: 552AN: 1461874Hom.: 3 Cov.: 31 AF XY: 0.000373 AC XY: 271AN XY: 727236
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GnomAD4 genome ? AF: 0.000781 AC: 119AN: 152278Hom.: 1 Cov.: 33 AF XY: 0.000752 AC XY: 56AN XY: 74458
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:2
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia | Jul 30, 2015 | - - |
Herpes simplex encephalitis, susceptibility to, 3 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 24, 2024 | - - |
TRAF3-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jun 05, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Pathogenic
DEOGEN2
Benign
T;T;T;.;T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Pathogenic
D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;.;N;N;.;.
MutationTaster
Benign
D;D;D;D;N
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;N;N;N
Sift
Benign
T;T;T;T;T;T
Sift4G
Benign
T;T;T;T;T;T
Polyphen
D;B;D;B;B;.
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at