Variant 19-49851345-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000391842.6(PTOV1):c.17G>A(p.Arg6His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000434 in 138,278 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. R6C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000043 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PTOV1
ENST00000391842.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.703

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 made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.20074138).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
PTOV1	NM_001394010.1 linkuse as main transcript	c.17G>A	p.Arg6His	missense_variant	1/12	ENST00000391842.6	NP_001380939.1
PTOV1-AS1	NR_040037.1 linkuse as main transcript	n.109+223C>T		intron_variant, non_coding_transcript_variant
PTOV1	NR_130963.2 linkuse as main transcript	n.251+390G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTOV1	ENST00000391842.6 linkuse as main transcript	c.17G>A	p.Arg6His	missense_variant	1/12	5	NM_001394010.1	ENSP00000375717	P1	Q86YD1-1
PTOV1-AS1	ENST00000596521.1 linkuse as main transcript	n.109+223C>T		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes

AF:

0.0000434

AC:

AN:

138278

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000109

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000152

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

939462

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

440630

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000434

AC:

AN:

138278

Hom.:

Cov.:

AF XY:

0.0000603

AC XY:

AN XY:

66354

show subpopulations

Gnomad4 AFR

AF:

0.000109

Gnomad4 AMR

AF:

0.000152

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000340

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 03, 2022

The c.17G>A (p.R6H) alteration is located in exon 1 (coding exon 1) of the PTOV1 gene. This alteration results from a G to A substitution at nucleotide position 17, causing the arginine (R) at amino acid position 6 to be replaced by a histidine (H). 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

Pathogenic

0.80

BayesDel_addAF

Benign

-0.012

BayesDel_noAF

Benign

-0.25

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.017

T;T;T

Eigen

Benign

0.0046

Eigen_PC

Benign

-0.0033

FATHMM_MKL

Benign

0.50

LIST_S2

Benign

0.66

T;.;.

M_CAP

Pathogenic

0.52

MetaRNN

Benign

0.20

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

N;N;N

MutationTaster

Benign

1.0

D;N

PrimateAI

Pathogenic

0.95

PROVEAN

Benign

0.37

N;.;.

REVEL

Benign

0.096

Sift

Pathogenic

0.0

D;.;.

Sift4G

Benign

0.15

T;T;T

Polyphen

0.99

D;D;D

Vest4

0.18

MutPred

0.22

Loss of methylation at R6 (P = 0.0211);Loss of methylation at R6 (P = 0.0211);Loss of methylation at R6 (P = 0.0211);

MVP

0.52

MPC

0.48

ClinPred

0.66

GERP RS

3.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.3

Varity_R

0.19

gMVP

0.28

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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