rs58277463

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_015650.4(TRAF3IP1):c.1246A>T(p.Thr416Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0604 in 1,613,720 control chromosomes in the GnomAD database, including 5,390 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T416I) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.12 ( 1766 hom., cov: 32)

Exomes 𝑓: 0.055 ( 3624 hom. )

Consequence

TRAF3IP1
NM_015650.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.401

Publications

11 publications found

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 Gene-Disease associations (from GenCC):

ciliopathy
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
Senior-Loken syndrome 9
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, PanelApp Australia
Senior-Loken syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
short rib-polydactyly syndrome, Majewski type
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

TRAF3IP1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004148662).

BP6

Variant 2-238344583-A-T is Benign according to our data. Variant chr2-238344583-A-T is described in ClinVar as Benign. ClinVar VariationId is 1167552.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.264 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015650.4. 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
	TRAF3IP1	NM_015650.4	MANE Select	c.1246A>T	p.Thr416Ser	missense	Exon 9 of 17	NP_056465.2
	TRAF3IP1	NM_001139490.1		c.1064-2872A>T		intron	N/A	NP_001132962.1	Q8TDR0-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TRAF3IP1	ENST00000373327.5	TSL:1 MANE Select	c.1246A>T	p.Thr416Ser	missense	Exon 9 of 17	ENSP00000362424.4	Q8TDR0-1
TRAF3IP1	ENST00000391993.7	TSL:1	c.1064-2872A>T		intron	N/A	ENSP00000375851.3	Q8TDR0-2
TRAF3IP1	ENST00000935943.1		c.1150A>T	p.Thr384Ser	missense	Exon 8 of 16	ENSP00000606002.1

Frequencies

GnomAD3 genomes

AF:

0.117

AC:

17732

AN:

152060

Hom.:

1761

Cov.:

show subpopulations

Gnomad AFR

AF:

0.268

Gnomad AMI

AF:

0.0285

Gnomad AMR

AF:

0.0818

Gnomad ASJ

AF:

0.0472

Gnomad EAS

AF:

0.103

Gnomad SAS

AF:

0.114

Gnomad FIN

AF:

0.114

Gnomad MID

AF:

0.0665

Gnomad NFE

AF:

0.0393

Gnomad OTH

AF:

0.0981

GnomAD2 exomes

AF:

0.0787

AC:

19793

AN:

251456

AF XY:

0.0752

show subpopulations

Gnomad AFR exome

AF:

0.269

Gnomad AMR exome

AF:

0.0752

Gnomad ASJ exome

AF:

0.0457

Gnomad EAS exome

AF:

0.110

Gnomad FIN exome

AF:

0.105

Gnomad NFE exome

AF:

0.0402

Gnomad OTH exome

AF:

0.0738

GnomAD4 exome

AF:

0.0545

AC:

79698

AN:

1461542

Hom.:

3624

Cov.:

AF XY:

0.0550

AC XY:

40014

AN XY:

727082

show subpopulations

African (AFR)

AF:

0.279

AC:

9329

AN:

33458

American (AMR)

AF:

0.0769

AC:

3438

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.0448

AC:

1170

AN:

26132

East Asian (EAS)

AF:

0.112

AC:

4456

AN:

39696

South Asian (SAS)

AF:

0.0984

AC:

8485

AN:

86246

European-Finnish (FIN)

AF:

0.103

AC:

5491

AN:

53420

Middle Eastern (MID)

AF:

0.0975

AC:

562

AN:

5766

European-Non Finnish (NFE)

AF:

0.0384

AC:

42741

AN:

1111714

Other (OTH)

AF:

0.0667

AC:

4026

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

3599

7198

10796

14395

17994

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1838

3676

5514

7352

9190

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.117

AC:

17764

AN:

152178

Hom.:

1766

Cov.:

AF XY:

0.119

AC XY:

8856

AN XY:

74404

show subpopulations

African (AFR)

AF:

0.268

AC:

11128

AN:

41490

American (AMR)

AF:

0.0819

AC:

1253

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0472

AC:

164

AN:

3472

East Asian (EAS)

AF:

0.103

AC:

531

AN:

5172

South Asian (SAS)

AF:

0.114

AC:

549

AN:

4814

European-Finnish (FIN)

AF:

0.114

AC:

1211

AN:

10608

Middle Eastern (MID)

AF:

0.0714

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0393

AC:

2676

AN:

68008

Other (OTH)

AF:

0.0971

AC:

205

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

725

1451

2176

2902

3627

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

180

360

540

720

900

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0514

Hom.:

286

Bravo

AF:

0.120

TwinsUK

AF:

0.0345

AC:

128

ALSPAC

AF:

0.0418

AC:

161

ESP6500AA

AF:

0.255

AC:

1124

ESP6500EA

AF:

0.0395

AC:

340

ExAC

AF:

0.0806

AC:

9787

Asia WGS

AF:

0.0980

AC:

340

AN:

3478

EpiCase

AF:

0.0423

EpiControl

AF:

0.0449

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

TRAF3IP1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.78

BayesDel_noAF

Benign

-0.75

CADD

Benign

3.5

(source)

DANN

Benign

0.52

DEOGEN2

Benign

0.0055

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.033

LIST_S2

Benign

0.49

MetaRNN

Benign

0.0041

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.69

PhyloP100

0.40

PrimateAI

Benign

0.27

PROVEAN

Benign

0.10

REVEL

Benign

0.028

Sift

Benign

0.20

Sift4G

Benign

0.48

Polyphen

0.011

Vest4

0.062

MPC

0.14

ClinPred

0.00071

GERP RS

3.1

Varity_R

0.041

gMVP

0.11

Mutation Taster

=98/2

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over