1-209763543-G-C

Position:

• chr1-209763543-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_025228.4(TRAF3IP3):​c.658G>C​(p.Asp220His) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: TRAF3IP3 NM_025228.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.11

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.33123457).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRAF3IP3	NM_025228.4	c.658G>C	p.Asp220His	missense_variant	8/17	ENST00000367025.8	NP_079504.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRAF3IP3	ENST00000367025.8	c.658G>C	p.Asp220His	missense_variant	8/17	1	NM_025228.4	ENSP00000355992.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 29, 2024

The c.658G>C (p.D220H) alteration is located in exon 8 (coding exon 6) of the TRAF3IP3 gene. This alteration results from a G to C substitution at nucleotide position 658, causing the aspartic acid (D) at amino acid position 220 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Benign	-0.016	T
BayesDel_noAF	Benign	-0.26
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.016	T;T;.;T
Eigen	Uncertain	0.61
Eigen_PC	Uncertain	0.60
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.90	D;.;D;D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.33	T;T;T;T
MetaSVM	Benign	-0.77	T
MutationAssessor	Uncertain	2.3	.;M;.;M
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-0.20	N;N;N;N
REVEL	Benign	0.12
Sift	Uncertain	0.025	D;D;D;D
Sift4G	Uncertain	0.059	T;D;D;D
Polyphen		0.98	D;D;D;D
Vest4		0.36
MutPred		0.23		.;Gain of MoRF binding (P = 0.2008);.;Gain of MoRF binding (P = 0.2008);
MVP		0.55
MPC		0.59
ClinPred		0.83	D
GERP RS		4.8
Varity_R		0.12
gMVP		0.22

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-209936888;