1-209772988-C-G

Position:

• chr1-209772988-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 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

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

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=0.39155465).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRAF3IP3	NM_025228.4	c.743C>G	p.Ser248Cys	missense_variant	9/17	ENST00000367025.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRAF3IP3	ENST00000367025.8	c.743C>G	p.Ser248Cys	missense_variant	9/17	1	NM_025228.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

Mar 20, 2023

The c.743C>G (p.S248C) alteration is located in exon 9 (coding exon 7) of the TRAF3IP3 gene. This alteration results from a C to G substitution at nucleotide position 743, causing the serine (S) at amino acid position 248 to be replaced by a cysteine (C). 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	0.10
BayesDel_addAF	Uncertain	0.053	T
BayesDel_noAF	Benign	-0.16
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Benign	0.047	T;T;.;T
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Benign	0.75	D
LIST_S2	Uncertain	0.88	D;.;D;D
M_CAP	Uncertain	0.097	D
MetaRNN	Benign	0.39	T;T;T;T
MetaSVM	Uncertain	0.086	D
MutationAssessor	Benign	1.8	.;L;.;L
MutationTaster	Benign	0.97	D;D;D;D;D;D;D
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.82	N;N;N;N
REVEL	Uncertain	0.34
Sift	Benign	0.10	T;T;T;T
Sift4G	Benign	0.095	T;T;T;T
Polyphen		1.0	D;D;D;D
Vest4		0.48
MutPred		0.28		.;Loss of disorder (P = 0.011);.;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

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-209946333;