Genetic Variant TRAF3IP3:c.1253-394T>A (chr1-209778921-T-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_025228.4(TRAF3IP3):c.1253-394T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0417 in 227,208 control chromosomes in the GnomAD database, including 912 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.041 ( 612 hom., cov: 32)

Exomes 𝑓: 0.043 ( 300 hom. )

Consequence

TRAF3IP3
NM_025228.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.933

Publications

1 publications found

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 was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.3 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRAF3IP3	NM_025228.4 link	c.1253-394T>A		intron_variant	Intron 13 of 16	ENST00000367025.8	NP_079504.2	Q9Y228-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRAF3IP3	ENST00000367025.8 link	c.1253-394T>A		intron_variant	Intron 13 of 16	1	NM_025228.4	ENSP00000355992.3		Q9Y228-1

Frequencies

GnomAD3 genomes

AF:

0.0412

AC:

6267

AN:

152158

Hom.:

606

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00671

Gnomad AMI

AF:

0.0318

Gnomad AMR

AF:

0.180

Gnomad ASJ

AF:

0.0150

Gnomad EAS

AF:

0.313

Gnomad SAS

AF:

0.0880

Gnomad FIN

AF:

0.0126

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0133

Gnomad OTH

AF:

0.0345

GnomAD4 exome

AF:

0.0428

AC:

3205

AN:

74930

Hom.:

300

Cov.:

AF XY:

0.0465

AC XY:

1858

AN XY:

39956

show subpopulations

African (AFR)

AF:

0.00340

AC:

AN:

1178

American (AMR)

AF:

0.198

AC:

753

AN:

3800

Ashkenazi Jewish (ASJ)

AF:

0.0163

AC:

AN:

1898

East Asian (EAS)

AF:

0.310

AC:

783

AN:

2524

South Asian (SAS)

AF:

0.0735

AC:

825

AN:

11218

European-Finnish (FIN)

AF:

0.0158

AC:

AN:

3490

Middle Eastern (MID)

AF:

0.00746

AC:

AN:

268

European-Non Finnish (NFE)

AF:

0.0134

AC:

626

AN:

46598

Other (OTH)

AF:

0.0319

AC:

126

AN:

3956

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

137

274

412

549

686

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

150

200

250

<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:

0.0412

AC:

6278

AN:

152278

Hom.:

612

Cov.:

AF XY:

0.0471

AC XY:

3505

AN XY:

74456

show subpopulations

African (AFR)

AF:

0.00669

AC:

278

AN:

41572

American (AMR)

AF:

0.181

AC:

2774

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.0150

AC:

AN:

3472

East Asian (EAS)

AF:

0.312

AC:

1612

AN:

5160

South Asian (SAS)

AF:

0.0872

AC:

420

AN:

4816

European-Finnish (FIN)

AF:

0.0126

AC:

134

AN:

10624

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0133

AC:

905

AN:

68030

Other (OTH)

AF:

0.0346

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

250

500

750

1000

1250

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

132

198

264

330

<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:

0.0228

Hom.:

Bravo

AF:

0.0532

Asia WGS

AF:

0.154

AC:

534

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

(source)

DANN

Benign

0.79

PhyloP100

0.93

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

Computational scores

Splicing

Publications

Other links and lift over