19-49854521-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000391842.6(PTOV1):​c.287G>T​(p.Ser96Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000198 in 1,613,116 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000019 ( 0 hom. )

Consequence

PTOV1
ENST00000391842.6 missense

Scores

1
10
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.35
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.125938).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PTOV1NM_001394010.1 linkuse as main transcriptc.287G>T p.Ser96Ile missense_variant 2/12 ENST00000391842.6 NP_001380939.1
PTOV1NR_130963.2 linkuse as main transcriptn.367G>T non_coding_transcript_exon_variant 2/13

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PTOV1ENST00000391842.6 linkuse as main transcriptc.287G>T p.Ser96Ile missense_variant 2/125 NM_001394010.1 ENSP00000375717 P1Q86YD1-1
ENST00000601211.1 linkuse as main transcriptn.95C>A non_coding_transcript_exon_variant 2/33

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152168
Hom.:
0
Cov.:
33
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:
0.000771
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000998
AC:
25
AN:
250538
Hom.:
0
AF XY:
0.0000811
AC XY:
11
AN XY:
135600
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00136
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000192
AC:
28
AN:
1460948
Hom.:
0
Cov.:
32
AF XY:
0.0000179
AC XY:
13
AN XY:
726810
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000680
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152168
Hom.:
0
Cov.:
33
AF XY:
0.0000269
AC XY:
2
AN XY:
74328
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000771
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000680
ExAC
AF:
0.0000989
AC:
12

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 GeneticsMay 03, 2023The c.287G>T (p.S96I) alteration is located in exon 2 (coding exon 2) of the PTOV1 gene. This alteration results from a G to T substitution at nucleotide position 287, causing the serine (S) at amino acid position 96 to be replaced by an isoleucine (I). 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
0.67
BayesDel_addAF
Benign
-0.080
T
BayesDel_noAF
Uncertain
0.080
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.10
T;.;.;T;T;T;T
Eigen
Uncertain
0.53
Eigen_PC
Uncertain
0.46
FATHMM_MKL
Uncertain
0.81
D
LIST_S2
Benign
0.77
T;T;T;T;.;.;T
M_CAP
Uncertain
0.23
D
MetaRNN
Benign
0.13
T;T;T;T;T;T;T
MetaSVM
Benign
-0.32
T
MutationAssessor
Benign
2.0
.;.;.;M;M;M;.
MutationTaster
Benign
0.96
D;D
PrimateAI
Uncertain
0.64
T
PROVEAN
Uncertain
-3.0
.;.;.;D;.;.;.
REVEL
Benign
0.18
Sift
Uncertain
0.0020
.;.;.;D;.;.;.
Sift4G
Uncertain
0.0040
D;D;D;D;D;D;D
Polyphen
1.0
.;.;.;D;D;D;.
Vest4
0.83, 0.83, 0.83, 0.83, 0.83
MutPred
0.40
.;.;.;Loss of disorder (P = 0.0652);Loss of disorder (P = 0.0652);Loss of disorder (P = 0.0652);.;
MVP
0.83
MPC
0.56
ClinPred
0.32
T
GERP RS
3.9
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.34
gMVP
0.61

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: rs765282722; hg19: chr19-50357778; API