Genetic Variant PTOV1:p.Ala7Val (chr19-49851348-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_001394010.1(PTOV1):c.20C>T(p.Ala7Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 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. A7D) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PTOV1
NM_001394010.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.242

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.15150815).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001394010.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PTOV1	NM_001394010.1	MANE Select	c.20C>T	p.Ala7Val	missense	Exon 1 of 12	NP_001380939.1	Q86YD1-1
PTOV1	NM_001305105.2		c.20C>T	p.Ala7Val	missense	Exon 1 of 13	NP_001292034.1	Q86YD1-1
PTOV1	NM_017432.5		c.20C>T	p.Ala7Val	missense	Exon 1 of 13	NP_059128.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PTOV1	ENST00000391842.6	TSL:5 MANE Select	c.20C>T	p.Ala7Val	missense	Exon 1 of 12	ENSP00000375717.1	Q86YD1-1
PTOV1	ENST00000599732.5	TSL:1	c.20C>T	p.Ala7Val	missense	Exon 1 of 13	ENSP00000469128.1	Q86YD1-1
PTOV1	ENST00000601675.5	TSL:1	c.20C>T	p.Ala7Val	missense	Exon 1 of 13	ENSP00000472816.1	Q86YD1-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

947012

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

444610

African (AFR)

AF:

0.00

AC:

AN:

18594

American (AMR)

AF:

0.00

AC:

AN:

4338

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

8786

East Asian (EAS)

AF:

0.00

AC:

AN:

12232

South Asian (SAS)

AF:

0.00

AC:

AN:

18346

European-Finnish (FIN)

AF:

0.00

AC:

AN:

11878

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2198

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

836204

Other (OTH)

AF:

0.00

AC:

AN:

34436

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.53

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.43

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.018

Eigen

Benign

-0.17

Eigen_PC

Benign

-0.14

FATHMM_MKL

Benign

0.30

LIST_S2

Benign

0.60

M_CAP

Pathogenic

0.46

MetaRNN

Benign

0.15

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PhyloP100

-0.24

PrimateAI

Pathogenic

0.90

PROVEAN

Benign

-0.10

REVEL

Benign

0.085

Sift

Pathogenic

0.0

Sift4G

Benign

0.071

Polyphen

0.86

Vest4

0.10

MutPred

0.19

Loss of methylation at R6 (P = 0.0834)

MVP

0.32

MPC

0.37

ClinPred

0.50

GERP RS

3.5

PromoterAI

-0.020

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.9

Varity_R

0.21

gMVP

0.25

Mutation Taster

=97/3

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over