10-87965536-CT-C

Position:

• chr10-87965536-CT-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_000314.8(PTEN):​c.*75del variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.000949 in 144,428 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00095 (0 hom., cov: 31)
  • Exomes 𝑓: 0.10 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PTEN NM_000314.8 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.80

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• BP6: Variant 10-87965536-CT-C is Benign according to our data. Variant chr10-87965536-CT-C is described in ClinVar as [Benign]. Clinvar id is 237636.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTEN	NM_000314.8	c.*75del		3_prime_UTR_variant	9/9	ENST00000371953.8
PTEN	NM_001304717.5	c.*75del		3_prime_UTR_variant	10/10
PTEN	NM_001304718.2	c.*75del		3_prime_UTR_variant	9/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTEN	ENST00000371953.8	c.*75del		3_prime_UTR_variant	9/9	1	NM_000314.8	P1

Frequencies

GnomAD3 genomes AF: 0.000935 AC: 135 AN: 144364 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000380

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00111

Gnomad ASJ AF: 0.000888

Gnomad EAS AF: 0.000199

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00459

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000887

Gnomad OTH AF: 0.000512

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.101 AC: 85462 AN: 847976 Hom.: 0 Cov.: 9 AF XY: 0.102 AC XY: 42834 AN XY: 419460

Gnomad4 AFR exome AF: 0.106

Gnomad4 AMR exome AF: 0.132

Gnomad4 ASJ exome AF: 0.124

Gnomad4 EAS exome AF: 0.109

Gnomad4 SAS exome AF: 0.117

Gnomad4 FIN exome AF: 0.108

Gnomad4 NFE exome AF: 0.0970

Gnomad4 OTH exome AF: 0.109

GnomAD4 genome AF: 0.000949 AC: 137 AN: 144428 Hom.: 0 Cov.: 31 AF XY: 0.00115 AC XY: 81 AN XY: 70182

Gnomad4 AFR AF: 0.000404

Gnomad4 AMR AF: 0.00110

Gnomad4 ASJ AF: 0.000888

Gnomad4 EAS AF: 0.000199

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00459

Gnomad4 NFE AF: 0.000887

Gnomad4 OTH AF: 0.000507

Alfa AF: 0.000216 Hom.: 0

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

PTEN hamartoma tumor syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 10, 2023

- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs878853930; hg19: chr10-89725293;