Variant chr19-49854970-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.451A>G(p.Thr151Ala) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000401 in 1,495,346 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000028 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000015 ( 0 hom. )

Consequence

PTOV1
ENST00000391842.6 missense, splice_region

Scores

Splicing: ADA: 0.0004095

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.874

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=0.14035985).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTOV1	NM_001394010.1 linkuse as main transcript	c.451A>G	p.Thr151Ala	missense_variant, splice_region_variant	5/12	ENST00000391842.6
PTOV1	NR_130963.2 linkuse as main transcript	n.531A>G		splice_region_variant, non_coding_transcript_exon_variant	5/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTOV1	ENST00000391842.6 linkuse as main transcript	c.451A>G	p.Thr151Ala	missense_variant, splice_region_variant	5/12	5	NM_001394010.1	P1	Q86YD1-1
	ENST00000601211.1 linkuse as main transcript			upstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0000279

AC:

AN:

143114

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000760

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:

0.0000153

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000445

AC:

AN:

224520

Hom.:

AF XY:

0.00000824

AC XY:

AN XY:

121348

show subpopulations

Gnomad AFR exome

AF:

0.0000724

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000148

AC:

AN:

1352100

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

670796

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000251

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:

9.56e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000279

AC:

AN:

143246

Hom.:

Cov.:

AF XY:

0.0000287

AC XY:

AN XY:

69578

show subpopulations

Gnomad4 AFR

AF:

0.0000758

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000153

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.00000825

AC:

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 12, 2023

The c.451A>G (p.T151A) alteration is located in exon 5 (coding exon 5) of the PTOV1 gene. This alteration results from a A to G substitution at nucleotide position 451, causing the threonine (T) at amino acid position 151 to be replaced by an alanine (A). 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

0.21

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.018

T;.;.;T;T;T

Eigen

Benign

-0.37

Eigen_PC

Benign

-0.27

FATHMM_MKL

Benign

0.61

LIST_S2

Benign

0.74

T;T;T;T;.;.

M_CAP

Uncertain

0.10

MetaRNN

Benign

0.14

T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

.;.;.;L;L;L

MutationTaster

Benign

0.99

D;D

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-1.6

.;.;.;N;.;.

REVEL

Benign

0.015

Sift

Benign

0.39

.;.;.;T;.;.

Sift4G

Uncertain

0.011

D;D;D;D;D;D

Polyphen

0.0

.;.;.;B;B;B

Vest4

0.38, 0.36, 0.33, 0.33, 0.33

MutPred

0.22

.;.;.;Loss of loop (P = 0.2237);Loss of loop (P = 0.2237);Loss of loop (P = 0.2237);

MVP

0.74

MPC

0.099

ClinPred

0.075

GERP RS

2.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.072

gMVP

0.43

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00041

dbscSNV1_RF

Benign

0.0080

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