19-49851377-C-G

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000391842.6(PTOV1):c.49C>G(p.Leu17Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000105 in 1,147,582 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000067 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

PTOV1
ENST00000391842.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.184

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.24457374).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	Protein	UniProt
PTOV1	NM_001305105.2 link	c.49C>G	p.Leu17Val	missense_variant	Exon 1 of 13	NP_001292034.1	Q86YD1-1
PTOV1	NM_001394010.1 link	c.49C>G	p.Leu17Val	missense_variant	Exon 1 of 12	NP_001380939.1
PTOV1	NM_017432.5 link	c.49C>G	p.Leu17Val	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.49C>G	p.Leu17Val	missense_variant	Exon 1 of 12	5		ENSP00000375717.1		Q86YD1-1

Frequencies

GnomAD3 genomes

AF:

0.00000672

AC:

AN:

148910

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:

0.0000150

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000110

AC:

AN:

998672

Hom.:

Cov.:

AF XY:

0.0000106

AC XY:

AN XY:

470154

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

19952

American (AMR)

AF:

0.00

AC:

AN:

5732

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

10692

East Asian (EAS)

AF:

0.00

AC:

AN:

18464

South Asian (SAS)

AF:

0.00

AC:

AN:

18822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

16566

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2468

European-Non Finnish (NFE)

AF:

0.0000127

AC:

AN:

868264

Other (OTH)

AF:

0.00

AC:

AN:

37712

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000672

AC:

AN:

148910

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

72620

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

40958

American (AMR)

AF:

0.00

AC:

AN:

15004

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3422

East Asian (EAS)

AF:

0.00

AC:

AN:

5130

South Asian (SAS)

AF:

0.00

AC:

AN:

4804

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9572

Middle Eastern (MID)

AF:

0.00

AC:

AN:

312

European-Non Finnish (NFE)

AF:

0.0000150

AC:

AN:

66754

Other (OTH)

AF:

0.00

AC:

AN:

2050

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 08, 2022

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.49C>G (p.L17V) alteration is located in exon 1 (coding exon 1) of the PTOV1 gene. This alteration results from a C to G substitution at nucleotide position 49, causing the leucine (L) at amino acid position 17 to be replaced by a valine (V). 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

0.078

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.39

CADD

Benign

(source)

DANN

Benign

0.88

DEOGEN2

Benign

0.016

T;T;T

Eigen

Benign

-0.074

Eigen_PC

Benign

-0.045

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.52

T;.;.

M_CAP

Pathogenic

0.54

MetaRNN

Benign

0.24

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

N;N;N

PhyloP100

-0.18

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

-0.20

N;.;.

REVEL

Benign

0.080

Sift

Pathogenic

0.0

D;.;.

Sift4G

Benign

0.20

T;T;T

Polyphen

0.88

P;P;P

Vest4

0.21

MutPred

0.18

Loss of catalytic residue at L17 (P = 0.2145);Loss of catalytic residue at L17 (P = 0.2145);Loss of catalytic residue at L17 (P = 0.2145);

MVP

0.37

MPC

0.33

ClinPred

0.39

GERP RS

3.5

PromoterAI

0.0083

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.9

Varity_R

0.30

gMVP

0.083

Mutation Taster

=90/10

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over