Genetic Variant PTOV1:p.Ala13Val (chr19-49851366-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The ENST00000391842.6(PTOV1):c.38C>T(p.Ala13Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000774 in 1,123,420 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A13D) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000066 ( 0 hom. )

Consequence

PTOV1
ENST00000391842.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.280

Publications

0 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.010636777).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	Protein	UniProt
PTOV1	NM_001305105.2 link	c.38C>T	p.Ala13Val	missense_variant	Exon 1 of 13	NP_001292034.1	Q86YD1-1
PTOV1	NM_001394010.1 link	c.38C>T	p.Ala13Val	missense_variant	Exon 1 of 12	NP_001380939.1
PTOV1	NM_017432.5 link	c.38C>T	p.Ala13Val	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.38C>T	p.Ala13Val	missense_variant	Exon 1 of 12	5		ENSP00000375717.1		Q86YD1-1

Frequencies

GnomAD3 genomes

AF:

0.000162

AC:

AN:

148374

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000979

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000401

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000833

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00323

Gnomad NFE

AF:

0.000135

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000656

AC:

AN:

974936

Hom.:

Cov.:

AF XY:

0.0000567

AC XY:

AN XY:

458584

show subpopulations

African (AFR)

AF:

0.000207

AC:

AN:

19308

American (AMR)

AF:

0.000783

AC:

AN:

5110

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

9838

East Asian (EAS)

AF:

0.00

AC:

AN:

15624

South Asian (SAS)

AF:

0.000215

AC:

AN:

18596

European-Finnish (FIN)

AF:

0.00

AC:

AN:

14510

Middle Eastern (MID)

AF:

0.00128

AC:

AN:

2352

European-Non Finnish (NFE)

AF:

0.0000410

AC:

AN:

853428

Other (OTH)

AF:

0.000387

AC:

AN:

36170

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.523

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000155

AC:

AN:

148484

Hom.:

Cov.:

AF XY:

0.000207

AC XY:

AN XY:

72480

show subpopulations

African (AFR)

AF:

0.0000976

AC:

AN:

40968

American (AMR)

AF:

0.000400

AC:

AN:

14984

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3414

East Asian (EAS)

AF:

0.00

AC:

AN:

5094

South Asian (SAS)

AF:

0.000626

AC:

AN:

4796

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9420

Middle Eastern (MID)

AF:

0.00345

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.000135

AC:

AN:

66548

Other (OTH)

AF:

0.00

AC:

AN:

2068

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000694

Hom.:

Bravo

AF:

0.000128

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.54

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.016

T;T;T

Eigen

Benign

-0.99

Eigen_PC

Benign

-0.96

FATHMM_MKL

Benign

0.065

LIST_S2

Benign

0.53

T;.;.

M_CAP

Pathogenic

0.41

MetaRNN

Benign

0.011

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

N;N;N

PhyloP100

0.28

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

0.070

N;.;.

REVEL

Benign

0.13

Sift

Pathogenic

0.0

D;.;.

Sift4G

Benign

0.85

T;T;T

Polyphen

0.0

B;B;B

Vest4

0.11

MutPred

0.15

Loss of relative solvent accessibility (P = 0.0676);Loss of relative solvent accessibility (P = 0.0676);Loss of relative solvent accessibility (P = 0.0676);

MVP

0.048

MPC

0.10

ClinPred

0.22

GERP RS

-1.4

PromoterAI

-0.063

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.6

Varity_R

0.16

gMVP

0.21

Mutation Taster

=98/2

polymorphism

(source)

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

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19-49851366-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over