rs2074238540

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The ENST00000391842.6(PTOV1):​c.52G>A​(p.Gly18Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000998 in 1,001,948 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000010 ( 0 hom. )

Consequence

PTOV1
ENST00000391842.6 missense

Scores

3
8
8

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.56

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-AS1 (HGNC:44174): (PTOV1 antisense RNA 1)

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PTOV1NM_001305105.2 linkc.52G>A p.Gly18Arg missense_variant Exon 1 of 13 NP_001292034.1 Q86YD1-1
PTOV1NM_001394010.1 linkc.52G>A p.Gly18Arg missense_variant Exon 1 of 12 NP_001380939.1
PTOV1NM_017432.5 linkc.52G>A p.Gly18Arg missense_variant Exon 1 of 13 NP_059128.2 Q86YD1-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PTOV1ENST00000391842.6 linkc.52G>A p.Gly18Arg missense_variant Exon 1 of 12 5 ENSP00000375717.1 Q86YD1-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
9.98e-7
AC:
1
AN:
1001948
Hom.:
0
Cov.:
32
AF XY:
0.00000212
AC XY:
1
AN XY:
471786
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
20102
American (AMR)
AF:
0.00
AC:
0
AN:
5786
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
10872
East Asian (EAS)
AF:
0.00
AC:
0
AN:
19000
South Asian (SAS)
AF:
0.0000530
AC:
1
AN:
18866
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
16780
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
2492
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
870126
Other (OTH)
AF:
0.00
AC:
0
AN:
37924
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<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
Cov.:
32
Alfa
AF:
0.00
Hom.:
0
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.44
BayesDel_addAF
Uncertain
0.036
T
BayesDel_noAF
Benign
-0.19
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.018
T;T;T
Eigen
Uncertain
0.20
Eigen_PC
Benign
0.18
FATHMM_MKL
Uncertain
0.87
D
LIST_S2
Benign
0.63
T;.;.
M_CAP
Pathogenic
0.59
D
MetaRNN
Uncertain
0.45
T;T;T
MetaSVM
Benign
-0.87
T
MutationAssessor
Benign
0.0
N;N;N
PhyloP100
1.6
PrimateAI
Pathogenic
0.93
D
PROVEAN
Benign
-0.47
N;.;.
REVEL
Uncertain
0.35
Sift
Pathogenic
0.0
D;.;.
Sift4G
Uncertain
0.010
D;D;D
Polyphen
1.0
D;D;D
Vest4
0.35
MutPred
0.21
Gain of methylation at G18 (P = 0.0032);Gain of methylation at G18 (P = 0.0032);Gain of methylation at G18 (P = 0.0032);
MVP
0.43
MPC
0.55
ClinPred
0.77
D
GERP RS
3.5
PromoterAI
-0.035
Neutral
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.9
Varity_R
0.18
gMVP
0.18
Mutation Taster
=89/11
polymorphism

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

Other links and lift over

dbSNP: rs2074238540; hg19: chr19-50354637; API