rs142350527
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_145725.3(TRAF3):c.189G>A(p.Pro63=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00471 in 1,614,160 control chromosomes in the GnomAD database, including 58 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0057 ( 9 hom., cov: 32)
Exomes 𝑓: 0.0046 ( 49 hom. )
Consequence
TRAF3
NM_145725.3 synonymous
NM_145725.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -4.18
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 -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.86).
BP6
?
Variant 14-102870390-G-A is Benign according to our data. Variant chr14-102870390-G-A is described in ClinVar as [Benign]. Clinvar id is 473289.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-102870390-G-A is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=-4.18 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.0046 (6726/1461832) while in subpopulation AMR AF= 0.0237 (1058/44720). AF 95% confidence interval is 0.0225. There are 49 homozygotes in gnomad4_exome. There are 3257 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
?
High AC in GnomAd4 at 871 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TRAF3 | NM_145725.3 | c.189G>A | p.Pro63= | synonymous_variant | 3/12 | ENST00000392745.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TRAF3 | ENST00000392745.8 | c.189G>A | p.Pro63= | synonymous_variant | 3/12 | 1 | NM_145725.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00572 AC: 871AN: 152210Hom.: 9 Cov.: 32
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GnomAD3 exomes AF: 0.00815 AC: 2045AN: 251054Hom.: 27 AF XY: 0.00726 AC XY: 986AN XY: 135744
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GnomAD4 exome AF: 0.00460 AC: 6726AN: 1461832Hom.: 49 Cov.: 31 AF XY: 0.00448 AC XY: 3257AN XY: 727216
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GnomAD4 genome ? AF: 0.00572 AC: 871AN: 152328Hom.: 9 Cov.: 32 AF XY: 0.00717 AC XY: 534AN XY: 74478
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Herpes simplex encephalitis, susceptibility to, 3 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 25, 2024 | - - |
TRAF3-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jun 27, 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
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BayesDel_noAF
Benign
CADD
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DANN
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at