10-87965536-CTT-CTTT

Position:

• chr10-87965536-CTT-CTTT

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.

The NM_000314.8(PTEN):​c.*75dupT variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.00143 in 144,684 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0014 (0 hom., cov: 31)
  • Exomes 𝑓: 0.069 (1 hom.)
  • Failed GnomAD Quality Control
• Consequence: PTEN NM_000314.8 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• 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]

PTEN (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTEN	NM_000314.8	c.*75dupT		3_prime_UTR_variant	9/9	ENST00000371953.8	NP_000305.3
PTEN	NM_001304717.5	c.*75dupT		3_prime_UTR_variant	10/10		NP_001291646.4
PTEN	NM_001304718.2	c.*75dupT		3_prime_UTR_variant	9/9		NP_001291647.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTEN	ENST00000371953.8	c.*75dupT		3_prime_UTR_variant	9/9	1	NM_000314.8	ENSP00000361021.3

Frequencies

GnomAD3 genomes AF: 0.00142 AC: 205 AN: 144622 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00167

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00117

Gnomad ASJ AF: 0.000591

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000660

Gnomad FIN AF: 0.00299

Gnomad MID AF: 0.00327

Gnomad NFE AF: 0.00134

Gnomad OTH AF: 0.000513

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0687 AC: 64355 AN: 937196 Hom.: 1 Cov.: 9 AF XY: 0.0682 AC XY: 31619 AN XY: 463718

Gnomad4 AFR exome AF: 0.0654

Gnomad4 AMR exome AF: 0.0702

Gnomad4 ASJ exome AF: 0.0731

Gnomad4 EAS exome AF: 0.0620

Gnomad4 SAS exome AF: 0.0701

Gnomad4 FIN exome AF: 0.0545

Gnomad4 NFE exome AF: 0.0695

Gnomad4 OTH exome AF: 0.0695

GnomAD4 genome AF: 0.00143 AC: 207 AN: 144684 Hom.: 0 Cov.: 31 AF XY: 0.00152 AC XY: 107 AN XY: 70312

Gnomad4 AFR AF: 0.00172

Gnomad4 AMR AF: 0.00117

Gnomad4 ASJ AF: 0.000591

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000662

Gnomad4 FIN AF: 0.00299

Gnomad4 NFE AF: 0.00134

Gnomad4 OTH AF: 0.000509

ClinVar

Not reported in ClinVar

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;