Genetic Variant PTOV1:p.Leu17Phe (chr19-49851377-C-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The ENST00000391842.6(PTOV1):c.49C>T(p.Leu17Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000002 in 998,672 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L17V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000020 ( 0 hom. )

Consequence

PTOV1
ENST00000391842.6 missense

Scores

Clinical Significance

Not reported in ClinVar

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.29291803).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	Protein	UniProt
PTOV1	NM_001305105.2 link	c.49C>T	p.Leu17Phe	missense_variant	Exon 1 of 13	NP_001292034.1	Q86YD1-1
PTOV1	NM_001394010.1 link	c.49C>T	p.Leu17Phe	missense_variant	Exon 1 of 12	NP_001380939.1
PTOV1	NM_017432.5 link	c.49C>T	p.Leu17Phe	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>T	p.Leu17Phe	missense_variant	Exon 1 of 12	5		ENSP00000375717.1		Q86YD1-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000200

AC:

AN:

998672

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

470154

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

19952

American (AMR)

AF:

0.000174

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:

0.00000115

AC:

AN:

868264

Other (OTH)

AF:

0.00

AC:

AN:

37712

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.42

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.016

T;T;T

Eigen

Benign

0.069

Eigen_PC

Benign

0.063

FATHMM_MKL

Benign

0.72

LIST_S2

Benign

0.46

T;.;.

M_CAP

Pathogenic

0.55

MetaRNN

Benign

0.29

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

N;N;N

PhyloP100

-0.18

PrimateAI

Pathogenic

0.90

PROVEAN

Benign

0.070

N;.;.

REVEL

Benign

0.10

Sift

Pathogenic

0.0

D;.;.

Sift4G

Benign

0.25

T;T;T

Polyphen

0.98

D;D;D

Vest4

0.24

MutPred

0.17

Gain of methylation at R22 (P = 0.2059);Gain of methylation at R22 (P = 0.2059);Gain of methylation at R22 (P = 0.2059);

MVP

0.49

MPC

0.46

ClinPred

0.53

GERP RS

3.5

PromoterAI

0.014

Neutral

(source)

Varity_R

0.25

gMVP

0.074

Mutation Taster

=92/8

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

Computational scores

Splicing

Publications

Other links and lift over