rs10489341

Positions:

• chr1-209758776-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001320143.2(TRAF3IP3):​c.-238C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 152,870 control chromosomes in the GnomAD database, including 2,025 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 0.10 (2022 hom., cov: 32)
  • Exomes 𝑓: 0.023 (3 hom.)
• Consequence: TRAF3IP3 NM_001320143.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.50

Genes affected

TRAF3IP3 (HGNC:30766): (TRAF3 interacting protein 3) The gene encodes a protein that mediates cell growth by modulating the c-Jun N-terminal kinase signal transduction pathway. The encoded protein may also interact with a large multi-protein assembly containing the phosphatase 2A catalytic subunit. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2013]

TRAF3IP3 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.299 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRAF3IP3	NM_025228.4	c.-159-258C>T		intron_variant		ENST00000367025.8	NP_079504.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRAF3IP3	ENST00000367025.8	c.-159-258C>T		intron_variant		1	NM_025228.4	ENSP00000355992.3

Frequencies

GnomAD3 genomes AF: 0.103 AC: 15597 AN: 151998 Hom.: 2022 Cov.: 32

Gnomad AFR AF: 0.304

Gnomad AMI AF: 0.0164

Gnomad AMR AF: 0.0522

Gnomad ASJ AF: 0.0118

Gnomad EAS AF: 0.0272

Gnomad SAS AF: 0.0814

Gnomad FIN AF: 0.00340

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0210

Gnomad OTH AF: 0.0829

GnomAD4 exome AF: 0.0225 AC: 17 AN: 754 Hom.: 3 Cov.: 0 AF XY: 0.0231 AC XY: 13 AN XY: 562

Gnomad4 AFR exome AF: 0.136

Gnomad4 AMR exome AF: 0.250

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0177

Gnomad4 OTH exome AF: 0.0500

GnomAD4 genome AF: 0.103 AC: 15620 AN: 152116 Hom.: 2022 Cov.: 32 AF XY: 0.0992 AC XY: 7378 AN XY: 74366

Gnomad4 AFR AF: 0.304

Gnomad4 AMR AF: 0.0521

Gnomad4 ASJ AF: 0.0118

Gnomad4 EAS AF: 0.0273

Gnomad4 SAS AF: 0.0813

Gnomad4 FIN AF: 0.00340

Gnomad4 NFE AF: 0.0210

Gnomad4 OTH AF: 0.0825

Alfa AF: 0.0348 Hom.: 704

Bravo AF: 0.114

Asia WGS AF: 0.0640 AC: 223 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.17
DANN	Benign	0.45

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

Publications

LitVar

Other links and lift over

dbSNP: rs10489341; hg19: chr1-209932121;