10-87891002-C-T

Variant names:

• chr10-87891002-C-T
• rs1234218
• NM_000314.8:c.80-3023C>T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_000314.8(PTEN):​c.80-3023C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0321 in 152,172 control chromosomes in the GnomAD database, including 113 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.032 (113 hom., cov: 31)
• Consequence: PTEN NM_000314.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.385

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0321 (4884/152172) while in subpopulation NFE AF= 0.0445 (3028/68000). AF 95% confidence interval is 0.0432. There are 113 homozygotes in gnomad4. There are 2389 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 113 SM gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTEN	NM_000314.8	c.80-3023C>T		intron_variant	Intron 1 of 8	ENST00000371953.8	NP_000305.3
PTEN	NM_001304717.5	c.599-3023C>T		intron_variant	Intron 2 of 9		NP_001291646.4
PTEN	NM_001304718.2	c.-626-3023C>T		intron_variant	Intron 1 of 8		NP_001291647.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTEN	ENST00000371953.8	c.80-3023C>T		intron_variant	Intron 1 of 8	1	NM_000314.8	ENSP00000361021.3

Frequencies

GnomAD3 genomes AF: 0.0321 AC: 4885 AN: 152054 Hom.: 113 Cov.: 31

Gnomad AFR AF: 0.00870

Gnomad AMI AF: 0.0735

Gnomad AMR AF: 0.0308

Gnomad ASJ AF: 0.0288

Gnomad EAS AF: 0.00673

Gnomad SAS AF: 0.0157

Gnomad FIN AF: 0.0630

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0445

Gnomad OTH AF: 0.0378

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0321 AC: 4884 AN: 152172 Hom.: 113 Cov.: 31 AF XY: 0.0321 AC XY: 2389 AN XY: 74388

Gnomad4 AFR AF: 0.00867

Gnomad4 AMR AF: 0.0308

Gnomad4 ASJ AF: 0.0288

Gnomad4 EAS AF: 0.00674

Gnomad4 SAS AF: 0.0156

Gnomad4 FIN AF: 0.0630

Gnomad4 NFE AF: 0.0445

Gnomad4 OTH AF: 0.0374

Alfa AF: 0.0387 Hom.: 22

Bravo AF: 0.0297

Asia WGS AF: 0.0110 AC: 39 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.6
DANN	Benign	0.74

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: rs1234218; hg19: chr10-89650759;