Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2
The NM_145725.3(TRAF3):c.1200C>A(p.Ala400Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000558 in 1,614,080 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. A400A) has been classified as Likely benign.
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]
TRAF3 Gene-Disease associations (from GenCC):
TRAF3 haploinsufficiency
Inheritance: AD Classification: MODERATE Submitted by: ClinGen
Our verdict: Benign. The variant received -11 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.73).
BP6
Variant 14-102905277-C-A is Benign according to our data. Variant chr14-102905277-C-A is described in CliVar as Likely_benign. Clinvar id is 573044.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-102905277-C-A is described in CliVar as Likely_benign. Clinvar id is 573044.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-102905277-C-A is described in CliVar as Likely_benign. Clinvar id is 573044.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-102905277-C-A is described in CliVar as Likely_benign. Clinvar id is 573044.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-102905277-C-A is described in CliVar as Likely_benign. Clinvar id is 573044.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-102905277-C-A is described in CliVar as Likely_benign. Clinvar id is 573044.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-102905277-C-A is described in CliVar as Likely_benign. Clinvar id is 573044.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-102905277-C-A is described in CliVar as Likely_benign. Clinvar id is 573044.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-102905277-C-A is described in CliVar as Likely_benign. Clinvar id is 573044.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-102905277-C-A is described in CliVar as Likely_benign. Clinvar id is 573044.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-102905277-C-A is described in CliVar as Likely_benign. Clinvar id is 573044.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-102905277-C-A is described in CliVar as Likely_benign. Clinvar id is 573044.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-102905277-C-A is described in CliVar as Likely_benign. Clinvar id is 573044.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-102905277-C-A is described in CliVar as Likely_benign. Clinvar id is 573044.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-102905277-C-A is described in CliVar as Likely_benign. Clinvar id is 573044.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-102905277-C-A is described in CliVar as Likely_benign. Clinvar id is 573044.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-102905277-C-A is described in CliVar as Likely_benign. Clinvar id is 573044.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-102905277-C-A is described in CliVar as Likely_benign. Clinvar id is 573044.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-102905277-C-A is described in CliVar as Likely_benign. Clinvar id is 573044.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-102905277-C-A is described in CliVar as Likely_benign. Clinvar id is 573044.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-102905277-C-A is described in CliVar as Likely_benign. Clinvar id is 573044.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-102905277-C-A is described in CliVar as Likely_benign. Clinvar id is 573044.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-102905277-C-A is described in CliVar as Likely_benign. Clinvar id is 573044.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-102905277-C-A is described in CliVar as Likely_benign. Clinvar id is 573044.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-102905277-C-A is described in CliVar as Likely_benign. Clinvar id is 573044.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-102905277-C-A is described in CliVar as Likely_benign. Clinvar id is 573044.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-1.9 with no splicing effect.