Variant 19-49851350-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The ENST00000391842.6(PTOV1):c.22C>T(p.Pro8Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000513 in 1,098,286 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P8L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0026 ( 1 hom., cov: 31)

Exomes 𝑓: 0.00019 ( 3 hom. )

Consequence

PTOV1
ENST00000391842.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.06

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:

PTOV1-AS1 (HGNC:44174): (PTOV1 antisense RNA 1)

PTOV1-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.024394542).

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
PTOV1	NM_001394010.1 linkuse as main transcript	c.22C>T	p.Pro8Ser	missense_variant	1/12	ENST00000391842.6	NP_001380939.1
PTOV1-AS1	NR_040037.1 linkuse as main transcript	n.109+218G>A		intron_variant, non_coding_transcript_variant
PTOV1	NR_130963.2 linkuse as main transcript	n.251+395C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTOV1	ENST00000391842.6 linkuse as main transcript	c.22C>T	p.Pro8Ser	missense_variant	1/12	5	NM_001394010.1	ENSP00000375717	P1	Q86YD1-1
PTOV1-AS1	ENST00000596521.1 linkuse as main transcript	n.109+218G>A		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes

AF:

0.00256

AC:

380

AN:

148246

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00899

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000535

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000451

Gnomad OTH

AF:

0.000982

GnomAD4 exome

AF:

0.000192

AC:

182

AN:

949932

Hom.:

Cov.:

AF XY:

0.000168

AC XY:

AN XY:

446146

show subpopulations

Gnomad4 AFR exome

AF:

0.00861

Gnomad4 AMR exome

AF:

0.000677

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000477

Gnomad4 OTH exome

AF:

0.000376

GnomAD4 genome

AF:

0.00257

AC:

381

AN:

148354

Hom.:

Cov.:

AF XY:

0.00250

AC XY:

181

AN XY:

72394

show subpopulations

Gnomad4 AFR

AF:

0.00898

Gnomad4 AMR

AF:

0.000534

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000451

Gnomad4 OTH

AF:

0.000972

Alfa

AF:

0.00192

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 11, 2021

The c.22C>T (p.P8S) alteration is located in exon 1 (coding exon 1) of the PTOV1 gene. This alteration results from a C to T substitution at nucleotide position 22, causing the proline (P) at amino acid position 8 to be replaced by a serine (S). 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

0.21

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.021

T;T;T

Eigen

Benign

-0.48

Eigen_PC

Benign

-0.36

FATHMM_MKL

Benign

0.40

LIST_S2

Benign

0.57

T;.;.

M_CAP

Pathogenic

0.49

MetaRNN

Benign

0.024

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

N;N;N

MutationTaster

Benign

1.0

D;N

PrimateAI

Pathogenic

0.91

PROVEAN

Benign

-0.60

N;.;.

REVEL

Benign

0.045

Sift

Benign

0.11

T;.;.

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

0.036

B;B;B

Vest4

0.10

MutPred

0.29

Gain of phosphorylation at P8 (P = 0.0019);Gain of phosphorylation at P8 (P = 0.0019);Gain of phosphorylation at P8 (P = 0.0019);

MVP

0.20

MPC

0.44

ClinPred

0.54

GERP RS

3.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.3

Varity_R

0.094

gMVP

0.23

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over