GeneBe

10-87925528-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 2P and 11B. PM2BP4_ModerateBP6_Very_StrongBP7

The NM_000314.8(PTEN):​c.180G>A​(p.Lys60Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000209 in 1,438,658 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

PTEN
NM_000314.8 synonymous

Scores

2

Clinical Significance

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

Conservation

PhyloP100: 2.47

Publications

1 publications found
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 Gene-Disease associations (from GenCC):
  • Cowden syndrome 1
    Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), G2P
  • PTEN hamartoma tumor syndrome
    Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
  • macrocephaly-autism syndrome
    Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Genomics England PanelApp, Orphanet
  • renal cell carcinoma
    Inheritance: AD Classification: MODERATE Submitted by: Genomics England PanelApp
  • leiomyosarcoma
    Inheritance: AR Classification: MODERATE Submitted by: Genomics England PanelApp
  • activated PI3K-delta syndrome
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • Bannayan-Riley-Ruvalcaba syndrome
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • Cowden disease
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • Lhermitte-Duclos disease
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • Proteus-like syndrome
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • glioma susceptibility 2
    Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.33).
BP6
Variant 10-87925528-G-A is Benign according to our data. Variant chr10-87925528-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 482075.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=2.47 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PTENNM_000314.8 linkc.180G>A p.Lys60Lys synonymous_variant Exon 3 of 9 ENST00000371953.8 NP_000305.3
PTENNM_001304717.5 linkc.699G>A p.Lys233Lys synonymous_variant Exon 4 of 10 NP_001291646.4
PTENNM_001304718.2 linkc.-541-5518G>A intron_variant Intron 2 of 8 NP_001291647.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PTENENST00000371953.8 linkc.180G>A p.Lys60Lys synonymous_variant Exon 3 of 9 1 NM_000314.8 ENSP00000361021.3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD2 exomes
AF:
0.00000417
AC:
1
AN:
239576
AF XY:
0.00
show subpopulations
Gnomad AFR exome
AF:
0.0000653
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000209
AC:
3
AN:
1438658
Hom.:
0
Cov.:
30
AF XY:
0.00000279
AC XY:
2
AN XY:
716598
show subpopulations
African (AFR)
AF:
0.0000302
AC:
1
AN:
33086
American (AMR)
AF:
0.00
AC:
0
AN:
44296
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25844
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39412
South Asian (SAS)
AF:
0.00
AC:
0
AN:
85428
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
46912
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5690
European-Non Finnish (NFE)
AF:
0.00000182
AC:
2
AN:
1098274
Other (OTH)
AF:
0.00
AC:
0
AN:
59716
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.442
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<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
Cov.:
32
Alfa
AF:
0.000218
Hom.:
0
Bravo
AF:
0.0000227

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

PTEN hamartoma tumor syndrome Benign:2
Dec 13, 2023
All of Us Research Program, National Institutes of Health
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

Jan 29, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

Hereditary cancer-predisposing syndrome Benign:2
May 03, 2016
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: seen in unaffected individuals, 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.

Apr 17, 2017
Color Diagnostics, LLC DBA Color Health
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

not specified Benign:1
May 23, 2025
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

Cowden syndrome 1 Benign:1
Feb 11, 2025
Myriad Genetics, Inc.
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

This variant is considered benign. This variant is a silent/synonymous amino acid change and it is not expected to impact splicing.

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.33
CADD
Benign
13
DANN
Benign
0.76
PhyloP100
2.5

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs972166984; hg19: chr10-89685285; API