19-49851393-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000391842.6(PTOV1):​c.65G>T​(p.Arg22Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000179 in 1,174,120 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000014 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000019 ( 0 hom. )

Consequence

PTOV1
ENST00000391842.6 missense

Scores

2
2
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.97
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)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PTOV1NM_001394010.1 linkuse as main transcriptc.65G>T p.Arg22Leu missense_variant 1/12 ENST00000391842.6 NP_001380939.1
PTOV1-AS1NR_040037.1 linkuse as main transcriptn.109+175C>A intron_variant, non_coding_transcript_variant
PTOV1NR_130963.2 linkuse as main transcriptn.251+438G>T intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PTOV1ENST00000391842.6 linkuse as main transcriptc.65G>T p.Arg22Leu missense_variant 1/125 NM_001394010.1 ENSP00000375717 P1Q86YD1-1
PTOV1-AS1ENST00000596521.1 linkuse as main transcriptn.109+175C>A intron_variant, non_coding_transcript_variant 1

Frequencies

GnomAD3 genomes
AF:
0.0000135
AC:
2
AN:
147906
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.0000300
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.0000185
AC:
19
AN:
1026120
Hom.:
0
Cov.:
32
AF XY:
0.0000207
AC XY:
10
AN XY:
483920
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000215
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000135
AC:
2
AN:
148000
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
72184
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000300
Gnomad4 OTH
AF:
0.00

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 GeneticsJan 19, 2024The c.65G>T (p.R22L) alteration is located in exon 1 (coding exon 1) of the PTOV1 gene. This alteration results from a G to T substitution at nucleotide position 65, causing the arginine (R) at amino acid position 22 to be replaced by a leucine (L). 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
Benign
0.18
BayesDel_addAF
Benign
-0.065
T
BayesDel_noAF
Benign
-0.33
CADD
Uncertain
24
DANN
Benign
0.95
DEOGEN2
Benign
0.018
T;T;T
Eigen
Benign
0.039
Eigen_PC
Benign
0.012
FATHMM_MKL
Benign
0.72
D
LIST_S2
Benign
0.63
T;.;.
M_CAP
Pathogenic
0.72
D
MetaRNN
Uncertain
0.44
T;T;T
MetaSVM
Benign
-0.96
T
MutationAssessor
Benign
0.0
N;N;N
MutationTaster
Benign
1.0
D;N
PrimateAI
Pathogenic
0.92
D
PROVEAN
Benign
-0.22
N;.;.
REVEL
Benign
0.26
Sift
Uncertain
0.018
D;.;.
Sift4G
Benign
0.29
T;T;T
Polyphen
0.96
D;D;D
Vest4
0.38
MutPred
0.27
Loss of methylation at R22 (P = 0.0109);Loss of methylation at R22 (P = 0.0109);Loss of methylation at R22 (P = 0.0109);
MVP
0.26
MPC
0.42
ClinPred
0.60
D
GERP RS
3.3
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
2.6
Varity_R
0.25
gMVP
0.39

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1379794257; hg19: chr19-50354650; API