rs33980500

Positions:

• chr6-111592059-C-A
• chr6-111592059-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_147686.4(TRAF3IP2):​c.28G>T​(p.Asp10Tyr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TRAF3IP2 NM_147686.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.11

Genes affected

TRAF3IP2 (HGNC:1343): (TRAF3 interacting protein 2) This gene encodes a protein involved in regulating responses to cytokines by members of the Rel/NF-kappaB transcription factor family. These factors play a central role in innate immunity in response to pathogens, inflammatory signals and stress. This gene product interacts with TRAF proteins (tumor necrosis factor receptor-associated factors) and either I-kappaB kinase or MAP kinase to activate either NF-kappaB or Jun kinase. Several alternative transcripts encoding different isoforms have been identified. Another transcript, which does not encode a protein and is transcribed in the opposite orientation, has been identified. Overexpression of this transcript has been shown to reduce expression of at least one of the protein encoding transcripts, suggesting it has a regulatory role in the expression of this gene. [provided by RefSeq, Aug 2009]

TRAF3IP2-AS1 (HGNC:40005): (TRAF3IP2 antisense RNA 1)

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.784

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRAF3IP2	NM_147686.4	c.28G>T	p.Asp10Tyr	missense_variant	2/9	ENST00000368761.11	NP_679211.2
TRAF3IP2-AS1	NR_034108.1	n.486-5779C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRAF3IP2	ENST00000368761.11	c.28G>T	p.Asp10Tyr	missense_variant	2/9	1	NM_147686.4	ENSP00000357750	P4
TRAF3IP2-AS1	ENST00000687951.2	n.446-5779C>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.55
BayesDel_addAF	Pathogenic	0.29	D
BayesDel_noAF	Pathogenic	0.17
CADD	Uncertain	26
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.45	.;.;T;T
Eigen	Pathogenic	0.75
Eigen_PC	Pathogenic	0.73
FATHMM_MKL	Benign	0.70	D
LIST_S2	Uncertain	0.87	D;D;.;D
M_CAP	Benign	0.064	D
MetaRNN	Pathogenic	0.78	D;D;D;D
MetaSVM	Benign	-0.50	T
MutationAssessor	Uncertain	2.0	.;.;M;M
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.74	T
PROVEAN	Uncertain	-2.4	N;N;N;.
REVEL	Benign	0.21
Sift	Pathogenic	0.0	D;D;D;.
Sift4G	Uncertain	0.035	D;D;D;D
Polyphen		1.0	D;.;D;D
Vest4		0.94
MutPred		0.26		.;.;Gain of sheet (P = 0.0125);Gain of sheet (P = 0.0125);
MVP		0.78
MPC		0.85
ClinPred		0.96	D
GERP RS		5.5
Varity_R		0.56
gMVP		0.61

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs33980500; hg19: chr6-111913262;