19-49854442-G-T

Variant summary

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

The ENST00000391842.6(PTOV1):​c.208G>T​(p.Gly70Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,650 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

PTOV1
ENST00000391842.6 missense

Scores

6
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.752
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=0.19150677).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PTOV1NM_001394010.1 linkuse as main transcriptc.208G>T p.Gly70Cys missense_variant 2/12 ENST00000391842.6 NP_001380939.1
PTOV1NR_130963.2 linkuse as main transcriptn.288G>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.208G>T p.Gly70Cys missense_variant 2/125 NM_001394010.1 ENSP00000375717 P1Q86YD1-1
ENST00000601211.1 linkuse as main transcriptn.161+13C>A intron_variant, non_coding_transcript_variant 3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.85e-7
AC:
1
AN:
1459650
Hom.:
0
Cov.:
32
AF XY:
0.00000138
AC XY:
1
AN XY:
726140
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:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

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 GeneticsAug 12, 2021The c.208G>T (p.G70C) 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 208, causing the glycine (G) at amino acid position 70 to be replaced by a cysteine (C). 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
0.12
BayesDel_addAF
Uncertain
0.013
T
BayesDel_noAF
Benign
-0.22
CADD
Benign
18
DANN
Uncertain
0.99
DEOGEN2
Benign
0.022
T;.;.;T;T;T;T
Eigen
Benign
-0.46
Eigen_PC
Benign
-0.48
FATHMM_MKL
Benign
0.53
D
LIST_S2
Benign
0.75
T;T;T;T;.;.;T
M_CAP
Uncertain
0.11
D
MetaRNN
Benign
0.19
T;T;T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.0
.;.;.;N;N;N;.
MutationTaster
Benign
0.99
N;N
PrimateAI
Uncertain
0.73
T
PROVEAN
Benign
-1.3
.;.;.;N;.;.;.
REVEL
Benign
0.13
Sift
Uncertain
0.0030
.;.;.;D;.;.;.
Sift4G
Uncertain
0.031
D;D;D;D;D;D;D
Polyphen
0.99
.;.;.;D;D;D;.
Vest4
0.50, 0.49, 0.52, 0.50
MutPred
0.26
.;.;.;Loss of glycosylation at S72 (P = 0.0493);Loss of glycosylation at S72 (P = 0.0493);Loss of glycosylation at S72 (P = 0.0493);.;
MVP
0.70
MPC
0.52
ClinPred
0.53
D
GERP RS
2.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.20
gMVP
0.40

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-50357699; API