NM_145725.3:c.*2589G>A

Variant names:

• chr14-102908373-G-A
• rs11160707
• NM_145725.3:c.*2589G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_145725.3(TRAF3):​c.*2589G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.019 in 152,688 control chromosomes in the GnomAD database, including 156 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.019 (156 hom., cov: 34)
  • Exomes 𝑓: 0.0034 (0 hom.)
• Consequence: TRAF3 NM_145725.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.120
• Publications: 7 publications found

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]

TRAF3 Gene-Disease associations (from GenCC):

• TRAF3 haploinsufficiency

  Inheritance: AD Classification: MODERATE Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.132 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145725.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAF3	NM_145725.3	MANE Select	c.*2589G>A		3_prime_UTR	Exon 12 of 12	NP_663777.1
	TRAF3	NM_003300.4		c.*2589G>A		3_prime_UTR	Exon 11 of 11	NP_003291.2
	TRAF3	NM_145726.3		c.*2589G>A		3_prime_UTR	Exon 11 of 11	NP_663778.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAF3	ENST00000392745.8	TSL:1 MANE Select	c.*2589G>A		3_prime_UTR	Exon 12 of 12	ENSP00000376500.3
	TRAF3	ENST00000560371.5	TSL:1	c.*2589G>A		3_prime_UTR	Exon 11 of 11	ENSP00000454207.1
	TRAF3	ENST00000351691.10	TSL:1	c.*2589G>A		3_prime_UTR	Exon 11 of 11	ENSP00000332468.5

Frequencies

GnomAD3 genomes AF: 0.0189 AC: 2878 AN: 152274 Hom.: 154 Cov.: 34

Gnomad AFR AF: 0.00393

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0921

Gnomad ASJ AF: 0.00605

Gnomad EAS AF: 0.140

Gnomad SAS AF: 0.0242

Gnomad FIN AF: 0.0154

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00347

Gnomad OTH AF: 0.0196

GnomAD4 exome AF: 0.00338 AC: 1 AN: 296 Hom.: 0 Cov.: 0 AF XY: 0.00450 AC XY: 1 AN XY: 222

African (AFR) AF: 0.00 AC: 0 AN: 10

American (AMR) AF: 0.00 AC: 0 AN: 4

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 6

South Asian (SAS) AF: 0.00 AC: 0 AN: 10

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 22

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 226

Other (OTH) AF: 0.0625 AC: 1 AN: 16

GnomAD4 genome AF: 0.0190 AC: 2893 AN: 152392 Hom.: 156 Cov.: 34 AF XY: 0.0209 AC XY: 1554 AN XY: 74518

African (AFR) AF: 0.00392 AC: 163 AN: 41598

American (AMR) AF: 0.0923 AC: 1414 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.00605 AC: 21 AN: 3472

East Asian (EAS) AF: 0.141 AC: 729 AN: 5186

South Asian (SAS) AF: 0.0240 AC: 116 AN: 4834

European-Finnish (FIN) AF: 0.0154 AC: 164 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00347 AC: 236 AN: 68038

Other (OTH) AF: 0.0236 AC: 50 AN: 2116

Alfa AF: 0.0104 Hom.: 47

Bravo AF: 0.0280

Asia WGS AF: 0.0830 AC: 286 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.1
DANN	Benign	0.82
PhyloP100		0.12
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs11160707; hg19: chr14-103374710;