Variant 19-49854442-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001364748.2(PTOV1):c.-216G>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,650 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 Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

PTOV1
NM_001364748.2 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.752

Variant links:

Genes affected

PTOV1 (HGNC:9632): (PTOV1 extended AT-hook containing adaptor protein) This gene encodes a protein that was found to be overexpressed in prostate adenocarcinomas. The encoded protein was found to interact with the lipid raft protein flotillin-1 and shuttle it from the cytoplasm to the nucleus in a cell cycle dependent manner. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Feb 2015]

PTOV1 links:

ENSG00000268047 (HGNC:):

ENSG00000268047 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.19150677).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	Protein
PTOV1	NM_001364748.2 link	c.-216G>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 2 of 13	NP_001351677.1
PTOV1	NM_001364750.2 link	c.-216G>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 2 of 13	NP_001351679.1
PTOV1	NM_001364747.2 link	c.253G>T	p.Gly85Cys	missense_variant	Exon 2 of 13	NP_001351676.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTOV1	ENST00000391842.6 link	c.208G>T	p.Gly70Cys	missense_variant	Exon 2 of 12	5		ENSP00000375717.1		Q86YD1-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1459650

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726140

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 12, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.208G>T (p.G70C) alteration is located in exon 2 (coding exon 2) of the PTOV1 gene. This alteration results from a G to T substitution at nucleotide position 208, causing the glycine (G) at amino acid position 70 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Uncertain

0.013

BayesDel_noAF

Benign

-0.22

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.022

T;.;.;T;T;T;T

Eigen

Benign

-0.46

Eigen_PC

Benign

-0.48

FATHMM_MKL

Benign

0.53

LIST_S2

Benign

0.75

T;T;T;T;.;.;T

M_CAP

Uncertain

0.11

MetaRNN

Benign

0.19

T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

.;.;.;N;N;N;.

PrimateAI

Uncertain

0.73

PROVEAN

Benign

-1.3

.;.;.;N;.;.;.

REVEL

Benign

0.13

Sift

Uncertain

0.0030

.;.;.;D;.;.;.

Sift4G

Uncertain

0.031

D;D;D;D;D;D;D

Polyphen

0.99

.;.;.;D;D;D;.

Vest4

0.50, 0.49, 0.52, 0.50

MutPred

0.26

.;.;.;Loss of glycosylation at S72 (P = 0.0493);Loss of glycosylation at S72 (P = 0.0493);Loss of glycosylation at S72 (P = 0.0493);.;

MVP

0.70

MPC

0.52

ClinPred

0.53

GERP RS

2.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.20

gMVP

0.40

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over