Variant 2-238320714-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_015650.4(TRAF3IP1):c.52C>T(p.Arg18Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000968 in 1,446,670 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

TRAF3IP1
NM_015650.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.22

Variant links:

Genes affected

TRAF3IP1 (HGNC:17861): (TRAF3 interacting protein 1) The protein encoded by this gene interacts with TNF receptor-associated factor 3, tethering it to cytoskeletal microtubules. The encoded protein is also an inhibitor of the innate type I IFN response. Defects in this gene are a cause of Senior-Loken syndrome 9. [provided by RefSeq, Mar 2017]

TRAF3IP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.3788985).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRAF3IP1	NM_015650.4 linkuse as main transcript	c.52C>T	p.Arg18Trp	missense_variant	1/17	ENST00000373327.5	NP_056465.2	Q8TDR0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TRAF3IP1	ENST00000373327.5 linkuse as main transcript	c.52C>T	p.Arg18Trp	missense_variant	1/17	1	NM_015650.4	ENSP00000362424.4	Q8TDR0-1
TRAF3IP1	ENST00000391993.7 linkuse as main transcript	c.52C>T	p.Arg18Trp	missense_variant	1/15	1		ENSP00000375851.3	Q8TDR0-2
TRAF3IP1	ENST00000409739.2 linkuse as main transcript	n.52C>T		non_coding_transcript_exon_variant	1/5	3		ENSP00000386648.2	H7BZ10

Frequencies

GnomAD3 genomes

AF:

0.00000661

AC:

AN:

151226

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000100

AC:

AN:

1295444

Hom.:

Cov.:

AF XY:

0.0000125

AC XY:

AN XY:

639178

show subpopulations

Gnomad4 AFR exome

AF:

0.0000383

Gnomad4 AMR exome

AF:

0.0000372

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:

0.0000108

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000661

AC:

AN:

151226

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73842

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 19, 2022

The c.52C>T (p.R18W) alteration is located in exon 1 (coding exon 1) of the TRAF3IP1 gene. This alteration results from a C to T substitution at nucleotide position 52, causing the arginine (R) at amino acid position 18 to be replaced by a tryptophan (W). 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

Pathogenic

0.70

BayesDel_addAF

Benign

-0.097

BayesDel_noAF

Benign

-0.38

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.084

.;T

Eigen

Uncertain

0.20

Eigen_PC

Benign

0.11

FATHMM_MKL

Benign

0.70

LIST_S2

Pathogenic

0.99

D;D

M_CAP

Uncertain

0.21

MetaRNN

Benign

0.38

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.0

M;M

PrimateAI

Pathogenic

0.89

PROVEAN

Pathogenic

-4.5

D;D

REVEL

Benign

0.14

Sift

Uncertain

0.0010

D;D

Sift4G

Pathogenic

0.0010

D;D

Polyphen

1.0

D;D

Vest4

0.32

MutPred

0.40

Loss of disorder (P = 0.0295);Loss of disorder (P = 0.0295);

MVP

0.33

MPC

0.47

ClinPred

0.91

GERP RS

1.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.1

Varity_R

0.31

gMVP

0.50

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

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