19-49857018-G-A
Position:
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
ENST00000391842.6 missense
Scores
7
8
4
Clinical Significance
Conservation
PhyloP100: 3.51
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]
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 | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PTOV1 | NM_001394010.1 | c.602G>A | p.Arg201His | missense_variant | 6/12 | ENST00000391842.6 | NP_001380939.1 | |
PTOV1-AS2 | NR_110730.1 | n.548C>T | non_coding_transcript_exon_variant | 5/5 | ||||
PTOV1 | NR_130963.2 | n.682G>A | non_coding_transcript_exon_variant | 6/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PTOV1 | ENST00000391842.6 | c.602G>A | p.Arg201His | missense_variant | 6/12 | 5 | NM_001394010.1 | ENSP00000375717 | P1 | |
PTOV1-AS2 | ENST00000593654.1 | n.548C>T | non_coding_transcript_exon_variant | 5/5 | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000920 AC: 14AN: 152194Hom.: 0 Cov.: 33
GnomAD3 genomes
AF:
AC:
14
AN:
152194
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.0000239 AC: 6AN: 251294Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135826
GnomAD3 exomes
AF:
AC:
6
AN:
251294
Hom.:
AF XY:
AC XY:
2
AN XY:
135826
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000233 AC: 34AN: 1461598Hom.: 0 Cov.: 31 AF XY: 0.0000193 AC XY: 14AN XY: 727112
GnomAD4 exome
AF:
AC:
34
AN:
1461598
Hom.:
Cov.:
31
AF XY:
AC XY:
14
AN XY:
727112
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.0000920 AC: 14AN: 152194Hom.: 0 Cov.: 33 AF XY: 0.0000942 AC XY: 7AN XY: 74344
GnomAD4 genome
AF:
AC:
14
AN:
152194
Hom.:
Cov.:
33
AF XY:
AC XY:
7
AN XY:
74344
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
ExAC
AF:
AC:
1
EpiCase
AF:
EpiControl
AF:
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 | Mar 20, 2023 | The 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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Benign
T;.;.;T;T;T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Pathogenic
D;D;D;D;.;.;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D;D;D;D;D;D
MetaSVM
Benign
T
MutationAssessor
Benign
.;.;.;L;L;L;.
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
.;.;.;D;.;.;.
REVEL
Uncertain
Sift
Uncertain
.;.;.;D;.;.;.
Sift4G
Pathogenic
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
MPC
0.56
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at