Genetic Variant NM_001394010.1:c.38C>T (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 NM_001394010.1(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. Variant has been reported in ClinVar as Uncertain significance (★). 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
NM_001394010.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

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:

Genome browser will be placed here

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).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001394010.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PTOV1	NM_001394010.1	MANE Select	c.38C>T	p.Ala13Val	missense	Exon 1 of 12	NP_001380939.1	Q86YD1-1
PTOV1	NM_001305105.2		c.38C>T	p.Ala13Val	missense	Exon 1 of 13	NP_001292034.1	Q86YD1-1
PTOV1	NM_017432.5		c.38C>T	p.Ala13Val	missense	Exon 1 of 13	NP_059128.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PTOV1	ENST00000391842.6	TSL:5 MANE Select	c.38C>T	p.Ala13Val	missense	Exon 1 of 12	ENSP00000375717.1	Q86YD1-1
PTOV1	ENST00000599732.5	TSL:1	c.38C>T	p.Ala13Val	missense	Exon 1 of 13	ENSP00000469128.1	Q86YD1-1
PTOV1	ENST00000601675.5	TSL:1	c.38C>T	p.Ala13Val	missense	Exon 1 of 13	ENSP00000472816.1	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

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000694

Hom.:

Bravo

AF:

0.000128

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

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

Eigen

Benign

-0.99

Eigen_PC

Benign

-0.96

FATHMM_MKL

Benign

0.065

LIST_S2

Benign

0.53

M_CAP

Pathogenic

0.41

MetaRNN

Benign

0.011

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PhyloP100

0.28

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

0.070

REVEL

Benign

0.13

Sift

Pathogenic

0.0

Sift4G

Benign

0.85

Polyphen

0.0

Vest4

0.11

MutPred

0.15

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over