Variant chr1-209760067-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_025228.4(TRAF3IP3):c.28C>T(p.Pro10Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,678 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

TRAF3IP3
NM_025228.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0440

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.096802026).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRAF3IP3	NM_025228.4 linkuse as main transcript	c.28C>T	p.Pro10Ser	missense_variant	3/17	ENST00000367025.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRAF3IP3	ENST00000367025.8 linkuse as main transcript	c.28C>T	p.Pro10Ser	missense_variant	3/17	1	NM_025228.4	P1	Q9Y228-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461678

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727110

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 09, 2023

The c.28C>T (p.P10S) alteration is located in exon 3 (coding exon 1) of the TRAF3IP3 gene. This alteration results from a C to T substitution at nucleotide position 28, causing the proline (P) at amino acid position 10 to be replaced by a serine (S). 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

0.091

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.013

T;T;T;.;T

Eigen

Benign

-0.38

Eigen_PC

Benign

-0.33

FATHMM_MKL

Benign

0.062

LIST_S2

Benign

0.73

T;.;T;T;T

M_CAP

Benign

0.0056

MetaRNN

Benign

0.097

T;T;T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

1.9

.;L;.;L;L

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Benign

0.41

PROVEAN

Benign

-0.91

N;N;D;N;N

REVEL

Benign

0.096

Sift

Uncertain

0.014

D;D;.;D;D

Sift4G

Uncertain

0.032

D;D;D;D;D

Polyphen

0.011

B;B;.;B;B

Vest4

0.15

MutPred

0.16

Gain of phosphorylation at P10 (P = 0.0152);Gain of phosphorylation at P10 (P = 0.0152);Gain of phosphorylation at P10 (P = 0.0152);Gain of phosphorylation at P10 (P = 0.0152);Gain of phosphorylation at P10 (P = 0.0152);

MVP

0.34

MPC

0.13

ClinPred

0.069

GERP RS

2.5

Varity_R

0.053

gMVP

0.15

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over