Variant 19-49854722-A-G 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.380A>G(p.Gln127Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,461,240 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

PTOV1
ENST00000391842.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0970

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:

(HGNC:):

links:

Genome browser will be placed here

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=0.16427818).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTOV1	NM_001394010.1 linkuse as main transcript	c.380A>G	p.Gln127Arg	missense_variant	3/12	ENST00000391842.6	NP_001380939.1
PTOV1	NR_130963.2 linkuse as main transcript	n.460A>G		non_coding_transcript_exon_variant	3/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTOV1	ENST00000391842.6 linkuse as main transcript	c.380A>G	p.Gln127Arg	missense_variant	3/12	5	NM_001394010.1	ENSP00000375717	P1	Q86YD1-1
	ENST00000601211.1 linkuse as main transcript	n.25-131T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000399

AC:

AN:

250770

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135738

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000883

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000616

AC:

AN:

1461240

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

726968

show subpopulations

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:

0.00000809

Gnomad4 OTH exome

AF:

0.00

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 16, 2023

The c.380A>G (p.Q127R) alteration is located in exon 3 (coding exon 3) of the PTOV1 gene. This alteration results from a A to G substitution at nucleotide position 380, causing the glutamine (Q) at amino acid position 127 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

Benign

0.17

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.027

T;.;.;T;T;T;T

Eigen

Benign

-0.15

Eigen_PC

Benign

-0.17

FATHMM_MKL

Benign

0.34

LIST_S2

Benign

0.70

T;T;T;T;.;.;T

M_CAP

Uncertain

0.16

MetaRNN

Benign

0.16

T;T;T;T;T;T;T

MetaSVM

Benign

-0.83

MutationAssessor

Benign

1.6

.;.;.;L;L;L;.

MutationTaster

Benign

0.77

D;D

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-1.9

.;.;.;N;.;.;.

REVEL

Benign

0.15

Sift

Benign

0.12

.;.;.;T;.;.;.

Sift4G

Benign

0.35

T;T;T;T;T;T;T

Polyphen

0.0

.;.;.;B;B;B;.

Vest4

0.26, 0.28, 0.29, 0.30, 0.29

MutPred

0.30

.;.;.;Gain of solvent accessibility (P = 0.0261);Gain of solvent accessibility (P = 0.0261);Gain of solvent accessibility (P = 0.0261);.;

MVP

0.70

MPC

0.11

ClinPred

0.63

GERP RS

-0.21

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.11

gMVP

0.58

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

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