rs3739070

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_015650.4(TRAF3IP1):c.1858A>C(p.Met620Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0759 in 1,607,770 control chromosomes in the GnomAD database, including 5,344 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.062 ( 386 hom., cov: 32)

Exomes 𝑓: 0.077 ( 4958 hom. )

Consequence

TRAF3IP1
NM_015650.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.126

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 Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0017504692).

BP6

Variant 2-238397627-A-C is Benign according to our data. Variant chr2-238397627-A-C is described in ClinVar as [Benign]. Clinvar id is 1166906.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0788 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRAF3IP1	NM_015650.4 link	c.1858A>C	p.Met620Leu	missense_variant	Exon 16 of 17	ENST00000373327.5	NP_056465.2	Q8TDR0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TRAF3IP1	ENST00000373327.5 link	c.1858A>C	p.Met620Leu	missense_variant	Exon 16 of 17	1	NM_015650.4	ENSP00000362424.4	Q8TDR0-1
TRAF3IP1	ENST00000391993.7 link	c.1660A>C	p.Met554Leu	missense_variant	Exon 14 of 15	1		ENSP00000375851.3	Q8TDR0-2
TRAF3IP1	ENST00000462122.1 link	n.869A>C		non_coding_transcript_exon_variant	Exon 7 of 7	3
TRAF3IP1	ENST00000483951.1 link	n.206A>C		non_coding_transcript_exon_variant	Exon 1 of 2	2

Frequencies

GnomAD3 genomes

AF:

0.0615

AC:

9313

AN:

151342

Hom.:

384

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0237

Gnomad AMI

AF:

0.0264

Gnomad AMR

AF:

0.0416

Gnomad ASJ

AF:

0.0479

Gnomad EAS

AF:

0.0457

Gnomad SAS

AF:

0.0453

Gnomad FIN

AF:

0.141

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0805

Gnomad OTH

AF:

0.0551

GnomAD3 exomes

AF:

0.0635

AC:

15763

AN:

248156

Hom.:

714

AF XY:

0.0645

AC XY:

8687

AN XY:

134602

show subpopulations

Gnomad AFR exome

AF:

0.0198

Gnomad AMR exome

AF:

0.0262

Gnomad ASJ exome

AF:

0.0415

Gnomad EAS exome

AF:

0.0385

Gnomad SAS exome

AF:

0.0397

Gnomad FIN exome

AF:

0.141

Gnomad NFE exome

AF:

0.0790

Gnomad OTH exome

AF:

0.0617

GnomAD4 exome

AF:

0.0774

AC:

112720

AN:

1456310

Hom.:

4958

Cov.:

AF XY:

0.0763

AC XY:

55314

AN XY:

724508

show subpopulations

Gnomad4 AFR exome

AF:

0.0212

Gnomad4 AMR exome

AF:

0.0306

Gnomad4 ASJ exome

AF:

0.0503

Gnomad4 EAS exome

AF:

0.0321

Gnomad4 SAS exome

AF:

0.0422

Gnomad4 FIN exome

AF:

0.147

Gnomad4 NFE exome

AF:

0.0835

Gnomad4 OTH exome

AF:

0.0688

GnomAD4 genome

AF:

0.0615

AC:

9322

AN:

151460

Hom.:

386

Cov.:

AF XY:

0.0625

AC XY:

4626

AN XY:

74008

show subpopulations

Gnomad4 AFR

AF:

0.0238

Gnomad4 AMR

AF:

0.0416

Gnomad4 ASJ

AF:

0.0479

Gnomad4 EAS

AF:

0.0456

Gnomad4 SAS

AF:

0.0455

Gnomad4 FIN

AF:

0.141

Gnomad4 NFE

AF:

0.0806

Gnomad4 OTH

AF:

0.0560

Alfa

AF:

0.0686

Hom.:

756

Bravo

AF:

0.0528

TwinsUK

AF:

0.0928

AC:

344

ALSPAC

AF:

0.0867

AC:

334

ESP6500AA

AF:

0.0234

AC:

103

ESP6500EA

AF:

0.0776

AC:

667

ExAC

AF:

0.0667

AC:

8093

Asia WGS

AF:

0.0370

AC:

127

AN:

3418

EpiCase

AF:

0.0712

EpiControl

AF:

0.0733

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 05, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 21835309) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.77

BayesDel_noAF

Benign

-0.81

CADD

Benign

DANN

Benign

0.58

DEOGEN2

Benign

0.0070

.;T

Eigen

Benign

-0.84

Eigen_PC

Benign

-0.61

FATHMM_MKL

Benign

0.42

LIST_S2

Benign

0.25

T;T

MetaRNN

Benign

0.0018

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-1.8

.;N

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.49

N;N

REVEL

Benign

0.052

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0

B;B

Vest4

0.098

MutPred

0.61

.;Loss of catalytic residue at M620 (P = 0.0267);

MPC

0.13

ClinPred

0.00022

GERP RS

2.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.038

gMVP

0.048

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