NM_025228.4:c.743C>G

Variant names:

• chr1-209772988-C-G
• NM_025228.4:c.743C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_025228.4(TRAF3IP3):​c.743C>G​(p.Ser248Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TRAF3IP3 NM_025228.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.21
• Publications: 0 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.39155465).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAF3IP3	NM_025228.4	MANE Select	c.743C>G	p.Ser248Cys	missense	Exon 9 of 17	NP_079504.2	Q9Y228-1
	TRAF3IP3	NM_001287754.2		c.-50C>G		5_prime_UTR_premature_start_codon_gain	Exon 2 of 7	NP_001274683.1	B1AJU2
	TRAF3IP3	NM_001320143.2		c.743C>G	p.Ser248Cys	missense	Exon 9 of 17	NP_001307072.1	Q9Y228-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAF3IP3	ENST00000367025.8	TSL:1 MANE Select	c.743C>G	p.Ser248Cys	missense	Exon 9 of 17	ENSP00000355992.3	Q9Y228-1
	TRAF3IP3	ENST00000367026.7	TSL:1	c.683C>G	p.Ser228Cys	missense	Exon 9 of 17	ENSP00000355993.3	Q9Y228-2
	TRAF3IP3	ENST00000478359.5	TSL:1	n.743C>G		non_coding_transcript_exon	Exon 9 of 13	ENSP00000417665.1	Q9Y228-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Uncertain	0.053	T
BayesDel_noAF	Benign	-0.16
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Benign	0.047	T
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Benign	0.75	D
LIST_S2	Uncertain	0.88	D
M_CAP	Uncertain	0.097	D
MetaRNN	Benign	0.39	T
MetaSVM	Uncertain	0.086	D
MutationAssessor	Benign	1.8	L
PhyloP100		1.2
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.82	N
REVEL	Uncertain	0.34
Sift	Benign	0.10	T
Sift4G	Benign	0.095	T
Polyphen		1.0	D
Vest4		0.48
MutPred		0.28		Loss of disorder (P = 0.011)
MVP		0.85
MPC		0.51
ClinPred		0.80	D
GERP RS		5.4
Varity_R		0.081
gMVP		0.12
Mutation Taster		=71/29	polymorphism

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

Other links and lift over

hg19: chr1-209946333;