chr10-87961150-T-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

This summary comes from the ClinGen Evidence Repository: PTEN c.1026+32T>G (IVS8+32T>G) meets criteria to be classified as benign for PTEN Hamartoma Tumor syndrome in an autosomal dominant manner using modified ACMG criteria (Mester et al. 2018; manuscript in preparation). Please see a summary of the rules and criteria codes in the “PTEN ACMG Specifications Summary” document (assertion method column).BA1: Allele frequency of 0.374 (37.4%, 102,771/274,696 alleles) in the gnomAD cohort. (PMID 27535533) LINK:https://erepo.genome.network/evrepo/ui/classification/CA000255/MONDO:0017623/003

Frequency

Genomes: 𝑓 0.40 ( 12672 hom., cov: 31)

Exomes 𝑓: 0.36 ( 93105 hom. )

Consequence

PTEN
NM_000314.8 intron

Scores

Clinical Significance

Benign reviewed by expert panel B:11

Conservation

PhyloP100: -0.850

Variant links:

Genes affected

PTEN (HGNC:9588): (phosphatase and tensin homolog) This gene was identified as a tumor suppressor that is mutated in a large number of cancers at high frequency. The protein encoded by this gene is a phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase. It contains a tensin like domain as well as a catalytic domain similar to that of the dual specificity protein tyrosine phosphatases. Unlike most of the protein tyrosine phosphatases, this protein preferentially dephosphorylates phosphoinositide substrates. It negatively regulates intracellular levels of phosphatidylinositol-3,4,5-trisphosphate in cells and functions as a tumor suppressor by negatively regulating AKT/PKB signaling pathway. The use of a non-canonical (CUG) upstream initiation site produces a longer isoform that initiates translation with a leucine, and is thought to be preferentially associated with the mitochondrial inner membrane. This longer isoform may help regulate energy metabolism in the mitochondria. A pseudogene of this gene is found on chromosome 9. Alternative splicing and the use of multiple translation start codons results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Feb 2015]

PTEN links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BA1

For more information check the summary or visit ClinGen Evidence Repository.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
PTEN	NM_000314.8 link	c.1026+32T>G	intron_variant	Intron 8 of 8	ENST00000371953.8	NP_000305.3
PTEN	NM_001304717.5 link	c.1545+32T>G	intron_variant	Intron 9 of 9		NP_001291646.4	P60484
PTEN	NM_001304718.2 link	c.435+32T>G	intron_variant	Intron 8 of 8		NP_001291647.1	P60484

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTEN	ENST00000371953.8 link	c.1026+32T>G		intron_variant	Intron 8 of 8	1	NM_000314.8	ENSP00000361021.3		P60484-1

Frequencies

GnomAD3 genomes

AF:

0.399

AC:

60661

AN:

151868

Hom.:

12632

Cov.:

show subpopulations

Gnomad AFR

AF:

0.501

Gnomad AMI

AF:

0.273

Gnomad AMR

AF:

0.451

Gnomad ASJ

AF:

0.377

Gnomad EAS

AF:

0.506

Gnomad SAS

AF:

0.300

Gnomad FIN

AF:

0.344

Gnomad MID

AF:

0.443

Gnomad NFE

AF:

0.336

Gnomad OTH

AF:

0.407

GnomAD2 exomes

AF:

0.373

AC:

92706

AN:

248338

AF XY:

0.363

show subpopulations

Gnomad AFR exome

AF:

0.498

Gnomad AMR exome

AF:

0.457

Gnomad ASJ exome

AF:

0.371

Gnomad EAS exome

AF:

0.489

Gnomad FIN exome

AF:

0.344

Gnomad NFE exome

AF:

0.335

Gnomad OTH exome

AF:

0.371

GnomAD4 exome

AF:

0.358

AC:

511154

AN:

1426510

Hom.:

93105

Cov.:

AF XY:

0.355

AC XY:

252501

AN XY:

711724

show subpopulations

African (AFR)

AF:

0.508

AC:

16594

AN:

32678

American (AMR)

AF:

0.462

AC:

20593

AN:

44616

Ashkenazi Jewish (ASJ)

AF:

0.370

AC:

9595

AN:

25940

East Asian (EAS)

AF:

0.500

AC:

19725

AN:

39422

South Asian (SAS)

AF:

0.307

AC:

26246

AN:

85374

European-Finnish (FIN)

AF:

0.342

AC:

18222

AN:

53350

Middle Eastern (MID)

AF:

0.408

AC:

2327

AN:

5704

European-Non Finnish (NFE)

AF:

0.348

AC:

375647

AN:

1080138

Other (OTH)

AF:

0.375

AC:

22205

AN:

59288

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

16157

32314

48470

64627

80784

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.400

AC:

60753

AN:

151986

Hom.:

12672

Cov.:

AF XY:

0.398

AC XY:

29556

AN XY:

74274

show subpopulations

African (AFR)

AF:

0.502

AC:

20795

AN:

41434

American (AMR)

AF:

0.452

AC:

6898

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.377

AC:

1305

AN:

3464

East Asian (EAS)

AF:

0.506

AC:

2622

AN:

5186

South Asian (SAS)

AF:

0.300

AC:

1449

AN:

4828

European-Finnish (FIN)

AF:

0.344

AC:

3624

AN:

10548

Middle Eastern (MID)

AF:

0.432

AC:

127

AN:

294

European-Non Finnish (NFE)

AF:

0.336

AC:

22812

AN:

67950

Other (OTH)

AF:

0.414

AC:

873

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1819

3638

5456

7275

9094

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.382

Hom.:

3937

Bravo

AF:

0.413

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: reviewed by expert panel

LINK: link

Submissions by phenotype

not provided

Benign:3

Apr 06, 2020

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

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

- -

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 30316882) -

not specified

Benign:2

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 70% of patients studied by a panel of primary immunodeficiencies. Number of patients: 62. Only high quality variants are reported. -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Cowden syndrome 1

Benign:2

Jul 07, 2023

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Oct 25, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

PTEN hamartoma tumor syndrome

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Sep 14, 2016

Clingen PTEN Variant Curation Expert Panel, Clingen

Significance:Benign

Review Status:reviewed by expert panel

Collection Method:curation

PTEN c.1026+32T>G (IVS8+32T>G) meets criteria to be classified as benign for PTEN Hamartoma Tumor syndrome in an autosomal dominant manner using modified ACMG criteria (Mester et al. 2018; manuscript in preparation). Please see a summary of the rules and criteria codes in the 'PTEN ACMG Specifications Summary' document (assertion method column). BA1: Allele frequency of 0.374 (37.4%, 102,771/274,696 alleles) in the gnomAD cohort. (PMID 27535533) -

Hereditary cancer-predisposing syndrome

Benign:1

Mar 26, 2020

Sema4, Sema4

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:curation

- -

Macrocephaly-autism syndrome

Benign:1

Oct 25, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.69

(source)

DANN

Benign

0.37

PhyloP100

-0.85

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

chr10-87961150-T-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over