2-238329333-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_015650.4(TRAF3IP1):c.906T>C(p.Pro302Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0588 in 1,357,820 control chromosomes in the GnomAD database, including 4,433 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. P302P) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.12 ( 1753 hom., cov: 32)

Exomes 𝑓: 0.052 ( 2680 hom. )

Consequence

TRAF3IP1
NM_015650.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.68

Publications

5 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):

Senior-Loken syndrome 9
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.97).

BP6

Variant 2-238329333-T-C is Benign according to our data. Variant chr2-238329333-T-C is described in ClinVar as Benign. ClinVar VariationId is 1167551.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.68 with no splicing effect.

BA1

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRAF3IP1	NM_015650.4 link	c.906T>C	p.Pro302Pro	synonymous_variant	Exon 5 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.906T>C	p.Pro302Pro	synonymous_variant	Exon 5 of 17	1	NM_015650.4	ENSP00000362424.4	Q8TDR0-1
TRAF3IP1	ENST00000391993.7 link	c.906T>C	p.Pro302Pro	synonymous_variant	Exon 5 of 15	1		ENSP00000375851.3	Q8TDR0-2
TRAF3IP1	ENST00000409739.2 link	n.*775T>C		non_coding_transcript_exon_variant	Exon 5 of 5	3		ENSP00000386648.2	H7BZ10
TRAF3IP1	ENST00000409739.2 link	n.*775T>C		3_prime_UTR_variant	Exon 5 of 5	3		ENSP00000386648.2	H7BZ10

Frequencies

GnomAD3 genomes

AF:

0.116

AC:

17696

AN:

151986

Hom.:

1748

Cov.:

show subpopulations

Gnomad AFR

AF:

0.268

Gnomad AMI

AF:

0.0285

Gnomad AMR

AF:

0.0815

Gnomad ASJ

AF:

0.0473

Gnomad EAS

AF:

0.103

Gnomad SAS

AF:

0.113

Gnomad FIN

AF:

0.114

Gnomad MID

AF:

0.0665

Gnomad NFE

AF:

0.0394

Gnomad OTH

AF:

0.0980

GnomAD2 exomes

AF:

0.0804

AC:

10662

AN:

132600

AF XY:

0.0752

show subpopulations

Gnomad AFR exome

AF:

0.263

Gnomad AMR exome

AF:

0.0730

Gnomad ASJ exome

AF:

0.0404

Gnomad EAS exome

AF:

0.107

Gnomad FIN exome

AF:

0.106

Gnomad NFE exome

AF:

0.0401

Gnomad OTH exome

AF:

0.0807

GnomAD4 exome

AF:

0.0516

AC:

62170

AN:

1205716

Hom.:

2680

Cov.:

AF XY:

0.0515

AC XY:

29862

AN XY:

579336

show subpopulations

African (AFR)

AF:

0.281

AC:

7295

AN:

25966

American (AMR)

AF:

0.0757

AC:

1566

AN:

20676

Ashkenazi Jewish (ASJ)

AF:

0.0422

AC:

686

AN:

16252

East Asian (EAS)

AF:

0.111

AC:

3634

AN:

32638

South Asian (SAS)

AF:

0.0967

AC:

3332

AN:

34464

European-Finnish (FIN)

AF:

0.101

AC:

4359

AN:

42964

Middle Eastern (MID)

AF:

0.100

AC:

476

AN:

4754

European-Non Finnish (NFE)

AF:

0.0384

AC:

37644

AN:

979310

Other (OTH)

AF:

0.0653

AC:

3178

AN:

48692

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

3237

6474

9710

12947

16184

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1772

3544

5316

7088

8860

<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:

17728

AN:

152104

Hom.:

1753

Cov.:

AF XY:

0.119

AC XY:

8838

AN XY:

74378

show subpopulations

African (AFR)

AF:

0.268

AC:

11105

AN:

41446

American (AMR)

AF:

0.0817

AC:

1248

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.0473

AC:

164

AN:

3470

East Asian (EAS)

AF:

0.102

AC:

529

AN:

5176

South Asian (SAS)

AF:

0.113

AC:

545

AN:

4818

European-Finnish (FIN)

AF:

0.114

AC:

1206

AN:

10596

Middle Eastern (MID)

AF:

0.0714

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0394

AC:

2679

AN:

68000

Other (OTH)

AF:

0.0970

AC:

205

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

722

1445

2167

2890

3612

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:

0.0453

Hom.:

116

Bravo

AF:

0.120

Asia WGS

AF:

0.0980

AC:

341

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

May 05, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

- -

TRAF3IP1-related disorder

Benign:1

Oct 21, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

0.047

(source)

DANN

Benign

0.16

PhyloP100

-2.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over