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GeneBe

19-49857018-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The ENST00000391842.6(PTOV1):c.602G>A(p.Arg201His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000297 in 1,613,792 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000023 ( 0 hom. )

Consequence

PTOV1
ENST00000391842.6 missense

Scores

7
5
3

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.51
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-AS2 (HGNC:51284): (PTOV1 antisense RNA 2)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.818

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PTOV1NM_001394010.1 linkuse as main transcriptc.602G>A p.Arg201His missense_variant 6/12 ENST00000391842.6
PTOV1-AS2NR_110730.1 linkuse as main transcriptn.548C>T non_coding_transcript_exon_variant 5/5
PTOV1NR_130963.2 linkuse as main transcriptn.682G>A non_coding_transcript_exon_variant 6/13

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PTOV1ENST00000391842.6 linkuse as main transcriptc.602G>A p.Arg201His missense_variant 6/125 NM_001394010.1 P1Q86YD1-1
PTOV1-AS2ENST00000593654.1 linkuse as main transcriptn.548C>T non_coding_transcript_exon_variant 5/52

Frequencies

GnomAD3 genomes
AF:
0.0000920
AC:
14
AN:
152194
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000265
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
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:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000239
AC:
6
AN:
251294
Hom.:
0
AF XY:
0.0000147
AC XY:
2
AN XY:
135826
show subpopulations
Gnomad AFR exome
AF:
0.0000615
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:
0.0000440
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000233
AC:
34
AN:
1461598
Hom.:
0
Cov.:
31
AF XY:
0.0000193
AC XY:
14
AN XY:
727112
show subpopulations
Gnomad4 AFR exome
AF:
0.000149
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.0000348
Gnomad4 FIN exome
AF:
0.0000187
Gnomad4 NFE exome
AF:
0.0000207
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000920
AC:
14
AN:
152194
Hom.:
0
Cov.:
33
AF XY:
0.0000942
AC XY:
7
AN XY:
74344
show subpopulations
Gnomad4 AFR
AF:
0.000265
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000113
Hom.:
0
Bravo
AF:
0.000106
ExAC
AF:
0.00000824
AC:
1
EpiCase
AF:
0.0000545
EpiControl
AF:
0.000119

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 submitterclinical testingAmbry GeneticsMar 20, 2023The c.602G>A (p.R201H) alteration is located in exon 6 (coding exon 6) of the PTOV1 gene. This alteration results from a G to A substitution at nucleotide position 602, causing the arginine (R) at amino acid position 201 to be replaced by a histidine (H). 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
0.93
BayesDel_addAF
Uncertain
0.13
D
BayesDel_noAF
Pathogenic
0.30
Cadd
Pathogenic
28
Dann
Pathogenic
1.0
DEOGEN2
Benign
0.16
T;.;.;T;T;T;T
Eigen
Uncertain
0.59
Eigen_PC
Uncertain
0.55
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Pathogenic
0.97
D;D;D;D;.;.;D
M_CAP
Uncertain
0.15
D
MetaRNN
Pathogenic
0.82
D;D;D;D;D;D;D
MetaSVM
Benign
-0.52
T
MutationTaster
Benign
1.0
D;D
PrimateAI
Pathogenic
0.84
D
Sift4G
Pathogenic
0.0
D;D;D;D;D;D;D
Polyphen
1.0
.;.;.;D;D;D;.
Vest4
0.82, 0.87, 0.90, 0.89
MutPred
0.70
.;.;.;Gain of catalytic residue at L203 (P = 0.0556);Gain of catalytic residue at L203 (P = 0.0556);Gain of catalytic residue at L203 (P = 0.0556);.;
MVP
0.87
MPC
0.56
ClinPred
0.85
D
GERP RS
3.3
Varity_R
0.24
gMVP
0.63

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.

Other links and lift over

dbSNP: rs761892225; hg19: chr19-50360275; COSMIC: COSV55589509; COSMIC: COSV55589509; API