10-87960876-CTTTTTTTTT-CTTTTTTT

Variant names:

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 2P and 12B. PM2BP6_Very_StrongBS1

The NM_000314.8(PTEN):c.802-4_802-3delTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00407 in 1,386,566 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 26)

Exomes 𝑓: 0.0045 ( 0 hom. )

Consequence

PTEN
NM_000314.8 splice_region, intron

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 1.37

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 -10 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP6

Variant 10-87960876-CTT-C is Benign according to our data. Variant chr10-87960876-CTT-C is described in ClinVar as [Likely_benign]. Clinvar id is 92833.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-87960876-CTT-C is described in Lovd as [Benign]. Variant chr10-87960876-CTT-C is described in Lovd as [Benign]. Variant chr10-87960876-CTT-C is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.00446 (5626/1261530) while in subpopulation AMR AF= 0.00811 (258/31804). AF 95% confidence interval is 0.0073. There are 0 homozygotes in gnomad4_exome. There are 2782 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
PTEN	NM_000314.8 link	c.802-4_802-3delTT	splice_region_variant, intron_variant	Intron 7 of 8	ENST00000371953.8	NP_000305.3
PTEN	NM_001304717.5 link	c.1321-4_1321-3delTT	splice_region_variant, intron_variant	Intron 8 of 9		NP_001291646.4	P60484
PTEN	NM_001304718.2 link	c.211-4_211-3delTT	splice_region_variant, intron_variant	Intron 7 of 8		NP_001291647.1	P60484

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTEN	ENST00000371953.8 link	c.802-17_802-16delTT		intron_variant	Intron 7 of 8	1	NM_000314.8	ENSP00000361021.3		P60484-1

Frequencies

GnomAD3 genomes

AF:

0.000120

AC:

AN:

125040

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000315

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000772

Gnomad ASJ

AF:

0.000325

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000433

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000153

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00446

AC:

5626

AN:

1261530

Hom.:

AF XY:

0.00443

AC XY:

2782

AN XY:

628200

show subpopulations

Gnomad4 AFR exome

AF:

0.00517

Gnomad4 AMR exome

AF:

0.00811

Gnomad4 ASJ exome

AF:

0.00536

Gnomad4 EAS exome

AF:

0.00257

Gnomad4 SAS exome

AF:

0.00533

Gnomad4 FIN exome

AF:

0.00531

Gnomad4 NFE exome

AF:

0.00427

Gnomad4 OTH exome

AF:

0.00442

GnomAD4 genome

AF:

0.000128

AC:

AN:

125036

Hom.:

Cov.:

AF XY:

0.000182

AC XY:

AN XY:

60370

show subpopulations

Gnomad4 AFR

AF:

0.0000629

Gnomad4 AMR

AF:

0.0000771

Gnomad4 ASJ

AF:

0.000325

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000433

Gnomad4 NFE

AF:

0.000153

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Mar 04, 2025

Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Hereditary cancer-predisposing syndrome

Benign:2

Jan 13, 2022

Sema4, Sema4

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: curation

- -

Jul 29, 2013

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Breast and/or ovarian cancer

Benign:1

Jun 29, 2021

CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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