rs10489341

Variant names:

• chr1-209758776-C-T
• rs10489341
• NM_025228.4:c.-159-258C>T

Variant summary

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

The NM_025228.4(TRAF3IP3):​c.-159-258C>T variant causes a intron 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_025228.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.50
• Publications: 2 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025228.4. 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
	TRAF3IP3	NM_025228.4	MANE Select	c.-159-258C>T		intron	N/A	NP_079504.2
	TRAF3IP3	NM_001320143.2		c.-238C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 17	NP_001307072.1
	TRAF3IP3	NM_001320143.2		c.-238C>T		5_prime_UTR	Exon 1 of 17	NP_001307072.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAF3IP3	ENST00000367025.8	TSL:1 MANE Select	c.-159-258C>T		intron	N/A	ENSP00000355992.3
	TRAF3IP3	ENST00000367026.7	TSL:1	c.-159-258C>T		intron	N/A	ENSP00000355993.3
	TRAF3IP3	ENST00000478359.5	TSL:1	n.-159-258C>T		intron	N/A	ENSP00000417665.1

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

African (AFR) AF: 0.136 AC: 3 AN: 22

American (AMR) AF: 0.250 AC: 1 AN: 4

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12

East Asian (EAS) AF: 0.00 AC: 0 AN: 22

South Asian (SAS) AF: 0.00 AC: 0 AN: 8

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 26

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.0177 AC: 11 AN: 620

Other (OTH) AF: 0.0500 AC: 2 AN: 40

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

African (AFR) AF: 0.304 AC: 12577 AN: 41424

American (AMR) AF: 0.0521 AC: 797 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0118 AC: 41 AN: 3472

East Asian (EAS) AF: 0.0273 AC: 141 AN: 5166

South Asian (SAS) AF: 0.0813 AC: 392 AN: 4822

European-Finnish (FIN) AF: 0.00340 AC: 36 AN: 10598

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0210 AC: 1427 AN: 68022

Other (OTH) AF: 0.0825 AC: 174 AN: 2108

Alfa AF: 0.0457 Hom.: 2471

Bravo AF: 0.114

Asia WGS AF: 0.0640 AC: 223 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.17
DANN	Benign	0.45
PhyloP100		-1.5
PromoterAI		-0.061	Neutral
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: rs10489341; hg19: chr1-209932121;