Variant 19-49851348-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBS1_SupportingBS2

The NM_017432.5(PTOV1):c.20C>A(p.Ala7Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00173 in 1,095,420 control chromosomes in the GnomAD database, including 26 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0084 ( 14 hom., cov: 31)

Exomes 𝑓: 0.00068 ( 12 hom. )

Consequence

PTOV1
NM_017432.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.242

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 Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.002914995).

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00844 (1252/148408) while in subpopulation AFR AF= 0.0292 (1194/40928). AF 95% confidence interval is 0.0278. There are 14 homozygotes in gnomad4. There are 597 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

BS2

High Homozygotes in GnomAd4 at 14 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	Protein	UniProt
PTOV1	NM_001305105.2 link	c.20C>A	p.Ala7Asp	missense_variant	1/13	NP_001292034.1	Q86YD1-1
PTOV1	NM_001394010.1 link	c.20C>A	p.Ala7Asp	missense_variant	1/12	NP_001380939.1
PTOV1	NM_017432.5 link	c.20C>A	p.Ala7Asp	missense_variant	1/13	NP_059128.2	Q86YD1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTOV1	ENST00000391842.6 link	c.20C>A	p.Ala7Asp	missense_variant	1/12	5		ENSP00000375717.1		Q86YD1-1

Frequencies

GnomAD3 genomes

AF:

0.00842

AC:

1249

AN:

148298

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0292

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00261

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00321

Gnomad NFE

AF:

0.0000300

Gnomad OTH

AF:

0.00739

GnomAD4 exome

AF:

0.000682

AC:

646

AN:

947012

Hom.:

Cov.:

AF XY:

0.000580

AC XY:

258

AN XY:

444610

show subpopulations

Gnomad4 AFR exome

AF:

0.0301

Gnomad4 AMR exome

AF:

0.00300

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:

0.0000144

Gnomad4 OTH exome

AF:

0.00174

GnomAD4 genome

AF:

0.00844

AC:

1252

AN:

148408

Hom.:

Cov.:

AF XY:

0.00825

AC XY:

597

AN XY:

72392

show subpopulations

Gnomad4 AFR

AF:

0.0292

Gnomad4 AMR

AF:

0.00260

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000209

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000300

Gnomad4 OTH

AF:

0.00730

Alfa

AF:

0.00687

Hom.:

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

Aug 21, 2024

The c.20C>A (p.A7D) alteration is located in exon 1 (coding exon 1) of the PTOV1 gene. This alteration results from a C to A substitution at nucleotide position 20, causing the alanine (A) at amino acid position 7 to be replaced by an aspartic acid (D). 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

0.64

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.023

T;T;T

Eigen

Benign

-0.10

Eigen_PC

Benign

-0.090

FATHMM_MKL

Benign

0.46

LIST_S2

Benign

0.50

T;.;.

MetaRNN

Benign

0.0029

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

N;N;N

PrimateAI

Pathogenic

0.92

PROVEAN

Benign

-0.63

N;.;.

REVEL

Benign

0.073

Sift

Pathogenic

0.0

D;.;.

Sift4G

Uncertain

0.027

D;D;D

Polyphen

0.96

P;P;P

Vest4

0.24

MutPred

0.17

Loss of methylation at R5 (P = 0.064);Loss of methylation at R5 (P = 0.064);Loss of methylation at R5 (P = 0.064);

MVP

0.36

MPC

0.57

ClinPred

0.55

GERP RS

3.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.9

Varity_R

0.57

gMVP

0.38

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