Variant 19-49851393-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_017432.5(PTOV1):c.65G>T(p.Arg22Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000179 in 1,174,120 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000019 ( 0 hom. )

Consequence

PTOV1
NM_017432.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.97

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	Protein	UniProt
PTOV1	NM_001305105.2 link	c.65G>T	p.Arg22Leu	missense_variant	Exon 1 of 13	NP_001292034.1	Q86YD1-1
PTOV1	NM_001394010.1 link	c.65G>T	p.Arg22Leu	missense_variant	Exon 1 of 12	NP_001380939.1
PTOV1	NM_017432.5 link	c.65G>T	p.Arg22Leu	missense_variant	Exon 1 of 13	NP_059128.2	Q86YD1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTOV1	ENST00000391842.6 link	c.65G>T	p.Arg22Leu	missense_variant	Exon 1 of 12	5		ENSP00000375717.1		Q86YD1-1

Frequencies

GnomAD3 genomes

AF:

0.0000135

AC:

AN:

147906

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000300

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000185

AC:

AN:

1026120

Hom.:

Cov.:

AF XY:

0.0000207

AC XY:

AN XY:

483920

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000215

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000135

AC:

AN:

148000

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

72184

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000300

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 19, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.65G>T (p.R22L) alteration is located in exon 1 (coding exon 1) of the PTOV1 gene. This alteration results from a G to T substitution at nucleotide position 65, causing the arginine (R) at amino acid position 22 to be replaced by a leucine (L). 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

0.18

BayesDel_addAF

Benign

-0.065

BayesDel_noAF

Benign

-0.33

CADD

Uncertain

DANN

Benign

0.95

DEOGEN2

Benign

0.018

T;T;T

Eigen

Benign

0.039

Eigen_PC

Benign

0.012

FATHMM_MKL

Benign

0.72

LIST_S2

Benign

0.63

T;.;.

M_CAP

Pathogenic

0.72

MetaRNN

Uncertain

0.44

T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.0

N;N;N

PrimateAI

Pathogenic

0.92

PROVEAN

Benign

-0.22

N;.;.

REVEL

Benign

0.26

Sift

Uncertain

0.018

D;.;.

Sift4G

Benign

0.29

T;T;T

Polyphen

0.96

D;D;D

Vest4

0.38

MutPred

0.27

Loss of methylation at R22 (P = 0.0109);Loss of methylation at R22 (P = 0.0109);Loss of methylation at R22 (P = 0.0109);

MVP

0.26

MPC

0.42

ClinPred

0.60

GERP RS

3.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.6

Varity_R

0.25

gMVP

0.39

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