rs12573787

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 1P and 18B. PP2BP4_ModerateBP6_Very_StrongBA1

The NM_001304717.5(PTEN):c.10G>A(p.Gly4Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.143 in 381,510 control chromosomes in the GnomAD database, including 4,826 homozygotes. In-silico tool predicts a benign outcome for this variant. 4/5 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.13 ( 1493 hom., cov: 31)

Exomes 𝑓: 0.15 ( 3333 hom. )

Consequence

PTEN
NM_001304717.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts P:1B:9

Conservation

PhyloP100: 2.14

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 made for transcript

Verdict is Benign. Variant got -17 ACMG points.

PP2

Missense variant in the PTEN gene, where missense mutations are typically associated with disease (based on misZ statistic). The gene has 209 curated pathogenic missense variants (we use a threshold of 10). The gene has 22 curated benign missense variants. Gene score misZ: 3.4883 (above the threshold of 3.09). Trascript score misZ: 4.001 (above the threshold of 3.09). GenCC associations: The gene is linked to Lhermitte-Duclos disease, Bannayan-Riley-Ruvalcaba syndrome, Proteus syndrome, macrocephaly-autism syndrome, Cowden syndrome 1, Cowden disease, Proteus-like syndrome, leiomyosarcoma, activated PI3K-delta syndrome, PTEN hamartoma tumor syndrome, glioma susceptibility 2, renal cell carcinoma.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.43).

BP6

Variant 10-87863959-G-A is Benign according to our data. Variant chr10-87863959-G-A is described in ClinVar as [Benign]. Clinvar id is 810888.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-87863959-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.335 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTEN	NM_000314.8 link	c.-511G>A		5_prime_UTR_variant	Exon 1 of 9	ENST00000371953.8	NP_000305.3
PTEN	NM_001304717.5 link	c.10G>A	p.Gly4Arg	missense_variant	Exon 1 of 10		NP_001291646.4	P60484
PTEN	NM_001304718.2 link	c.-1216G>A		5_prime_UTR_variant	Exon 1 of 9		NP_001291647.1	P60484

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTEN	ENST00000371953 link	c.-511G>A		5_prime_UTR_variant	Exon 1 of 9	1	NM_000314.8	ENSP00000361021.3		P60484-1

Frequencies

GnomAD3 genomes

AF:

0.126

AC:

18970

AN:

150292

Hom.:

1491

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0614

Gnomad AMI

AF:

0.0592

Gnomad AMR

AF:

0.193

Gnomad ASJ

AF:

0.121

Gnomad EAS

AF:

0.349

Gnomad SAS

AF:

0.124

Gnomad FIN

AF:

0.109

Gnomad MID

AF:

0.134

Gnomad NFE

AF:

0.138

Gnomad OTH

AF:

0.139

GnomAD4 exome

AF:

0.154

AC:

35529

AN:

231108

Hom.:

3333

Cov.:

AF XY:

0.152

AC XY:

18136

AN XY:

119532

show subpopulations

Gnomad4 AFR exome

AF:

0.0618

Gnomad4 AMR exome

AF:

0.213

Gnomad4 ASJ exome

AF:

0.112

Gnomad4 EAS exome

AF:

0.349

Gnomad4 SAS exome

AF:

0.130

Gnomad4 FIN exome

AF:

0.113

Gnomad4 NFE exome

AF:

0.135

Gnomad4 OTH exome

AF:

0.154

GnomAD4 genome

AF:

0.126

AC:

18981

AN:

150402

Hom.:

1493

Cov.:

AF XY:

0.127

AC XY:

9318

AN XY:

73528

show subpopulations

Gnomad4 AFR

AF:

0.0615

Gnomad4 AMR

AF:

0.193

Gnomad4 ASJ

AF:

0.121

Gnomad4 EAS

AF:

0.349

Gnomad4 SAS

AF:

0.124

Gnomad4 FIN

AF:

0.109

Gnomad4 NFE

AF:

0.138

Gnomad4 OTH

AF:

0.138

Alfa

AF:

0.0599

Hom.:

Bravo

AF:

0.131

Asia WGS

AF:

0.212

AC:

730

AN:

3438

ClinVar

Significance: Benign

Submissions summary: Pathogenic:1Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Mar 04, 2025

Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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 41% of patients studied by a panel of primary immunodeficiencies. Number of patients: 36. Only high quality variants are reported. -

not provided

Benign:3

Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Nov 23, 2024

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

- -

Myeloproliferative neoplasm, unclassifiable

Pathogenic:1

Aug 25, 2022

Dept. of Cytogenetics, ICMR- National Institute of Immunohaematology

Significance: Likely pathogenic

Review Status: flagged submission

Collection Method: clinical testing

- -

PTEN-related disorder

Benign:1

Mar 19, 2020

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). -

PTEN hamartoma tumor syndrome

Benign:1

Oct 26, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Macrocephaly-autism syndrome;C2751642:Glioma susceptibility 2;C2931456:Familial prostate cancer;C3551915:Familial meningioma;CN072330:Cowden syndrome 1

Benign:1

Apr 24, 2023

Department of Pathology and Laboratory Medicine, Sinai Health System

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: research

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Uncertain

0.99

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over