Genetic Variant PTOV1:p.Gly18Arg (chr19-49851380-G-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The ENST00000391842.6(PTOV1):c.52G>C(p.Gly18Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000998 in 1,001,948 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000010 ( 0 hom. )

Consequence

PTOV1
ENST00000391842.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.56

Publications

0 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 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.52G>C	p.Gly18Arg	missense_variant	Exon 1 of 13	NP_001292034.1	Q86YD1-1
PTOV1	NM_001394010.1 link	c.52G>C	p.Gly18Arg	missense_variant	Exon 1 of 12	NP_001380939.1
PTOV1	NM_017432.5 link	c.52G>C	p.Gly18Arg	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.52G>C	p.Gly18Arg	missense_variant	Exon 1 of 12	5		ENSP00000375717.1		Q86YD1-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

9.98e-7

AC:

AN:

1001948

Hom.:

Cov.:

AF XY:

0.00000212

AC XY:

AN XY:

471786

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

20102

American (AMR)

AF:

0.000173

AC:

AN:

5786

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

10872

East Asian (EAS)

AF:

0.00

AC:

AN:

19000

South Asian (SAS)

AF:

0.00

AC:

AN:

18866

European-Finnish (FIN)

AF:

0.00

AC:

AN:

16780

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2492

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

870126

Other (OTH)

AF:

0.00

AC:

AN:

37924

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

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

Apr 11, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.52G>C (p.G18R) alteration is located in exon 1 (coding exon 1) of the PTOV1 gene. This alteration results from a G to C substitution at nucleotide position 52, causing the glycine (G) at amino acid position 18 to be replaced by an arginine (R). 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

Uncertain

0.44

BayesDel_addAF

Uncertain

0.036

BayesDel_noAF

Benign

-0.19

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.018

T;T;T

Eigen

Uncertain

0.20

Eigen_PC

Benign

0.19

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.63

T;.;.

M_CAP

Pathogenic

0.53

MetaRNN

Uncertain

0.43

T;T;T

MetaSVM

Benign

-0.87

MutationAssessor

Benign

0.0

N;N;N

PhyloP100

1.6

PrimateAI

Pathogenic

0.93

PROVEAN

Benign

-0.47

N;.;.

REVEL

Uncertain

0.37

Sift

Pathogenic

0.0

D;.;.

Sift4G

Uncertain

0.010

D;D;D

Polyphen

1.0

D;D;D

Vest4

0.35

MutPred

0.21

Gain of methylation at G18 (P = 0.0032);Gain of methylation at G18 (P = 0.0032);Gain of methylation at G18 (P = 0.0032);

MVP

0.43

MPC

0.55

ClinPred

0.74

GERP RS

3.5

PromoterAI

0.074

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.9

Varity_R

0.18

gMVP

0.18

Mutation Taster

=89/11

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over