Variant 19-49851344-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_017432.5(PTOV1):c.16C>T(p.Arg6Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000213 in 941,014 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 (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

PTOV1
NM_017432.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.668

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=0.2269859).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	Protein	UniProt
PTOV1	NM_001305105.2 link	c.16C>T	p.Arg6Cys	missense_variant	Exon 1 of 13	NP_001292034.1	Q86YD1-1
PTOV1	NM_001394010.1 link	c.16C>T	p.Arg6Cys	missense_variant	Exon 1 of 12	NP_001380939.1
PTOV1	NM_017432.5 link	c.16C>T	p.Arg6Cys	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.16C>T	p.Arg6Cys	missense_variant	Exon 1 of 12	5		ENSP00000375717.1		Q86YD1-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000213

AC:

AN:

941014

Hom.:

Cov.:

AF XY:

0.00000226

AC XY:

AN XY:

441612

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000240

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:

0.00000120

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 26, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.16C>T (p.R6C) alteration is located in exon 1 (coding exon 1) of the PTOV1 gene. This alteration results from a C to T substitution at nucleotide position 16, causing the arginine (R) at amino acid position 6 to be replaced by a cysteine (C). 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

0.91

BayesDel_addAF

Uncertain

0.037

BayesDel_noAF

Benign

-0.18

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.024

T;T;T

Eigen

Benign

0.035

Eigen_PC

Benign

0.0083

FATHMM_MKL

Benign

0.31

LIST_S2

Benign

0.72

T;.;.

M_CAP

Pathogenic

0.54

MetaRNN

Benign

0.23

T;T;T

MetaSVM

Benign

-0.86

MutationAssessor

Benign

0.0

N;N;N

PrimateAI

Pathogenic

0.96

PROVEAN

Benign

-1.6

N;.;.

REVEL

Benign

0.20

Sift

Pathogenic

0.0

D;.;.

Sift4G

Uncertain

0.037

D;D;D

Polyphen

1.0

D;D;D

Vest4

0.27

MutPred

0.27

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

0.35

MPC

0.52

ClinPred

0.75

GERP RS

3.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.9

Varity_R

0.30

gMVP

0.31

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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