NM_001031685.3:c.685C>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_001031685.3(TP53BP2):c.685C>A(p.Gln229Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0814 in 1,613,248 control chromosomes in the GnomAD database, including 5,962 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.061 ( 378 hom., cov: 32)

Exomes 𝑓: 0.084 ( 5584 hom. )

Consequence

TP53BP2
NM_001031685.3 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 9.57

Publications

16 publications found

Variant links:

Genes affected

TP53BP2 (HGNC:12000): (tumor protein p53 binding protein 2) This gene encodes a member of the ASPP (apoptosis-stimulating protein of p53) family of p53 interacting proteins. The protein contains four ankyrin repeats and an SH3 domain involved in protein-protein interactions. It is localized to the perinuclear region of the cytoplasm, and regulates apoptosis and cell growth through interactions with other regulatory molecules including members of the p53 family. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

TP53BP2 Gene-Disease associations (from GenCC):

open-angle glaucoma
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
Tourette syndrome
Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

TP53BP2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0053198636).

BP6

Variant 1-223803417-G-T is Benign according to our data. Variant chr1-223803417-G-T is described in ClinVar as Benign. ClinVar VariationId is 3057025.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0872 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001031685.3. 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
	TP53BP2	NM_001031685.3	MANE Select	c.685C>A	p.Gln229Lys	missense	Exon 7 of 18	NP_001026855.2	Q13625-3
	TP53BP2	NM_005426.3		c.298C>A	p.Gln100Lys	missense	Exon 8 of 19	NP_005417.1	Q13625-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TP53BP2	ENST00000343537.12	TSL:1 MANE Select	c.685C>A	p.Gln229Lys	missense	Exon 7 of 18	ENSP00000341957.7	Q13625-3
TP53BP2	ENST00000391878.6	TSL:1	c.298C>A	p.Gln100Lys	missense	Exon 8 of 19	ENSP00000375750.2	Q13625-2
TP53BP2	ENST00000863548.1		c.679C>A	p.Gln227Lys	missense	Exon 7 of 18	ENSP00000533607.1

Frequencies

GnomAD3 genomes

AF:

0.0610

AC:

9276

AN:

152048

Hom.:

378

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0171

Gnomad AMI

AF:

0.0877

Gnomad AMR

AF:

0.0456

Gnomad ASJ

AF:

0.0740

Gnomad EAS

AF:

0.0191

Gnomad SAS

AF:

0.0521

Gnomad FIN

AF:

0.0924

Gnomad MID

AF:

0.0886

Gnomad NFE

AF:

0.0891

Gnomad OTH

AF:

0.0575

GnomAD2 exomes

AF:

0.0659

AC:

16509

AN:

250604

AF XY:

0.0677

show subpopulations

Gnomad AFR exome

AF:

0.0127

Gnomad AMR exome

AF:

0.0359

Gnomad ASJ exome

AF:

0.0754

Gnomad EAS exome

AF:

0.0161

Gnomad FIN exome

AF:

0.0852

Gnomad NFE exome

AF:

0.0894

Gnomad OTH exome

AF:

0.0715

GnomAD4 exome

AF:

0.0835

AC:

122018

AN:

1461082

Hom.:

5584

Cov.:

AF XY:

0.0829

AC XY:

60247

AN XY:

726862

show subpopulations

African (AFR)

AF:

0.0145

AC:

485

AN:

33454

American (AMR)

AF:

0.0381

AC:

1699

AN:

44610

Ashkenazi Jewish (ASJ)

AF:

0.0770

AC:

2010

AN:

26116

East Asian (EAS)

AF:

0.0139

AC:

551

AN:

39668

South Asian (SAS)

AF:

0.0546

AC:

4701

AN:

86168

European-Finnish (FIN)

AF:

0.0871

AC:

4651

AN:

53388

Middle Eastern (MID)

AF:

0.0817

AC:

469

AN:

5740

European-Non Finnish (NFE)

AF:

0.0926

AC:

102895

AN:

1111580

Other (OTH)

AF:

0.0755

AC:

4557

AN:

60358

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

5489

10977

16466

21954

27443

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3750

7500

11250

15000

18750

<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:

0.0609

AC:

9271

AN:

152166

Hom.:

378

Cov.:

AF XY:

0.0603

AC XY:

4484

AN XY:

74382

show subpopulations

African (AFR)

AF:

0.0171

AC:

709

AN:

41538

American (AMR)

AF:

0.0456

AC:

697

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.0740

AC:

257

AN:

3472

East Asian (EAS)

AF:

0.0191

AC:

AN:

5180

South Asian (SAS)

AF:

0.0522

AC:

251

AN:

4812

European-Finnish (FIN)

AF:

0.0924

AC:

978

AN:

10580

Middle Eastern (MID)

AF:

0.0782

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0891

AC:

6057

AN:

67998

Other (OTH)

AF:

0.0569

AC:

120

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

440

881

1321

1762

2202

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

224

336

448

560

<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:

0.0757

Hom.:

739

Bravo

AF:

0.0556

TwinsUK

AF:

0.0793

AC:

294

ALSPAC

AF:

0.104

AC:

401

ESP6500AA

AF:

0.0148

AC:

ESP6500EA

AF:

0.0885

AC:

761

ExAC

AF:

0.0659

AC:

8000

Asia WGS

AF:

0.0280

AC:

AN:

3478

EpiCase

AF:

0.0938

EpiControl

AF:

0.0912

ClinVar

ClinVar submissions

Significance:Benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

TP53BP2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.33

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

Eigen

Pathogenic

0.92

Eigen_PC

Pathogenic

0.94

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.97

MetaRNN

Benign

0.0053

MetaSVM

Benign

-1.2

PhyloP100

9.6

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-1.6

REVEL

Benign

0.24

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.0080

Vest4

0.45

MPC

0.78

ClinPred

0.022

GERP RS

6.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

gMVP

0.20

Mutation Taster

=79/21

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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