10-87893929-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000314.8(PTEN):c.80-96A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.349 in 896,268 control chromosomes in the GnomAD database, including 58,190 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.39 ( 11905 hom., cov: 31)

Exomes 𝑓: 0.34 ( 46285 hom. )

Consequence

PTEN
NM_000314.8 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.751

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BP6

Variant 10-87893929-A-G is Benign according to our data. Variant chr10-87893929-A-G is described in ClinVar as [Benign]. Clinvar id is 440219.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.491 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
PTEN	NM_000314.8 linkuse as main transcript	c.80-96A>G	intron_variant	ENST00000371953.8
PTEN	NM_001304717.5 linkuse as main transcript	c.599-96A>G	intron_variant
PTEN	NM_001304718.2 linkuse as main transcript	c.-625-96A>G	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTEN	ENST00000371953.8 linkuse as main transcript	c.80-96A>G		intron_variant		1	NM_000314.8	P1	P60484-1

Frequencies

GnomAD3 genomes

AF:

0.387

AC:

57488

AN:

148358

Hom.:

11868

Cov.:

show subpopulations

Gnomad AFR

AF:

0.472

Gnomad AMI

AF:

0.272

Gnomad AMR

AF:

0.445

Gnomad ASJ

AF:

0.376

Gnomad EAS

AF:

0.508

Gnomad SAS

AF:

0.299

Gnomad FIN

AF:

0.337

Gnomad MID

AF:

0.445

Gnomad NFE

AF:

0.328

Gnomad OTH

AF:

0.396

GnomAD4 exome

AF:

0.342

AC:

255591

AN:

747792

Hom.:

46285

AF XY:

0.338

AC XY:

132741

AN XY:

392880

show subpopulations

Gnomad4 AFR exome

AF:

0.469

Gnomad4 AMR exome

AF:

0.454

Gnomad4 ASJ exome

AF:

0.363

Gnomad4 EAS exome

AF:

0.501

Gnomad4 SAS exome

AF:

0.303

Gnomad4 FIN exome

AF:

0.326

Gnomad4 NFE exome

AF:

0.323

Gnomad4 OTH exome

AF:

0.361

GnomAD4 genome

AF:

0.388

AC:

57574

AN:

148476

Hom.:

11905

Cov.:

AF XY:

0.387

AC XY:

28054

AN XY:

72584

show subpopulations

Gnomad4 AFR

AF:

0.472

Gnomad4 AMR

AF:

0.446

Gnomad4 ASJ

AF:

0.376

Gnomad4 EAS

AF:

0.507

Gnomad4 SAS

AF:

0.298

Gnomad4 FIN

AF:

0.337

Gnomad4 NFE

AF:

0.328

Gnomad4 OTH

AF:

0.403

Alfa

AF:

0.333

Hom.:

8803

Bravo

AF:

0.393

Asia WGS

AF:

0.443

AC:

1538

AN:

3470

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Apr 06, 2020	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 32% of patients studied by a panel of primary immunodeficiencies. Number of patients: 28. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

Cadd

Benign

0.59

Dann

Benign

0.69

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