19-49857000-T-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000391842.6(PTOV1):ā€‹c.584T>Cā€‹(p.Ile195Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,228 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 33)
Exomes š‘“: 6.8e-7 ( 0 hom. )

Consequence

PTOV1
ENST00000391842.6 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.178
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-AS2 (HGNC:51284): (PTOV1 antisense RNA 2)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.050928712).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PTOV1NM_001394010.1 linkuse as main transcriptc.584T>C p.Ile195Thr missense_variant 6/12 ENST00000391842.6 NP_001380939.1
PTOV1-AS2NR_110730.1 linkuse as main transcriptn.566A>G non_coding_transcript_exon_variant 5/5
PTOV1NR_130963.2 linkuse as main transcriptn.664T>C non_coding_transcript_exon_variant 6/13

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PTOV1ENST00000391842.6 linkuse as main transcriptc.584T>C p.Ile195Thr missense_variant 6/125 NM_001394010.1 ENSP00000375717 P1Q86YD1-1
PTOV1-AS2ENST00000593654.1 linkuse as main transcriptn.566A>G non_coding_transcript_exon_variant 5/52

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461228
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
726928
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:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
EpiCase
AF:
0.0000545
EpiControl
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 GeneticsMar 24, 2023The c.584T>C (p.I195T) alteration is located in exon 6 (coding exon 6) of the PTOV1 gene. This alteration results from a T to C substitution at nucleotide position 584, causing the isoleucine (I) at amino acid position 195 to be replaced by a threonine (T). 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
Uncertain
0.42
BayesDel_addAF
Benign
-0.073
T
BayesDel_noAF
Benign
-0.34
CADD
Benign
18
DANN
Benign
0.85
DEOGEN2
Benign
0.0032
T;.;.;T;T;T;T
Eigen
Benign
-0.67
Eigen_PC
Benign
-0.47
FATHMM_MKL
Benign
0.53
D
LIST_S2
Benign
0.80
T;T;T;T;.;.;T
M_CAP
Benign
0.018
T
MetaRNN
Benign
0.051
T;T;T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.0
.;.;.;N;N;N;.
MutationTaster
Benign
0.70
N;N
PrimateAI
Uncertain
0.64
T
PROVEAN
Benign
1.1
.;.;.;N;.;.;.
REVEL
Benign
0.10
Sift
Benign
0.96
.;.;.;T;.;.;.
Sift4G
Benign
1.0
T;T;T;T;T;T;T
Polyphen
0.062
.;.;.;B;B;B;.
Vest4
0.33, 0.34, 0.32, 0.32
MutPred
0.30
.;.;.;Gain of catalytic residue at I195 (P = 0.0607);Gain of catalytic residue at I195 (P = 0.0607);Gain of catalytic residue at I195 (P = 0.0607);.;
MVP
0.39
MPC
0.14
ClinPred
0.081
T
GERP RS
4.3
Varity_R
0.051
gMVP
0.24

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.050
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: chr19-50360257; API