19-49851344-C-T

Variant summary

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

The ENST00000391842.6(PTOV1):​c.16C>T​(p.Arg6Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000213 in 941,014 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R6H) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

PTOV1
ENST00000391842.6 missense

Scores

4
3
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.668
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 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.2269859).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PTOV1NM_001394010.1 linkuse as main transcriptc.16C>T p.Arg6Cys missense_variant 1/12 ENST00000391842.6 NP_001380939.1
PTOV1-AS1NR_040037.1 linkuse as main transcriptn.109+224G>A intron_variant, non_coding_transcript_variant
PTOV1NR_130963.2 linkuse as main transcriptn.251+389C>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.16C>T p.Arg6Cys missense_variant 1/125 NM_001394010.1 ENSP00000375717 P1Q86YD1-1
PTOV1-AS1ENST00000596521.1 linkuse as main transcriptn.109+224G>A intron_variant, non_coding_transcript_variant 1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
AF:
0.00000213
AC:
2
AN:
941014
Hom.:
0
Cov.:
32
AF XY:
0.00000226
AC XY:
1
AN XY:
441612
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000240
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:
0.00000120
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
31
Bravo
AF:
0.0000113

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 26, 2022The c.16C>T (p.R6C) alteration is located in exon 1 (coding exon 1) of the PTOV1 gene. This alteration results from a C to T substitution at nucleotide position 16, causing the arginine (R) at amino acid position 6 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
Pathogenic
0.91
BayesDel_addAF
Uncertain
0.037
T
BayesDel_noAF
Benign
-0.18
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.024
T;T;T
Eigen
Benign
0.035
Eigen_PC
Benign
0.0083
FATHMM_MKL
Benign
0.31
N
LIST_S2
Benign
0.72
T;.;.
M_CAP
Pathogenic
0.54
D
MetaRNN
Benign
0.23
T;T;T
MetaSVM
Benign
-0.86
T
MutationAssessor
Benign
0.0
N;N;N
MutationTaster
Benign
0.99
D;D
PrimateAI
Pathogenic
0.96
D
PROVEAN
Benign
-1.6
N;.;.
REVEL
Benign
0.20
Sift
Pathogenic
0.0
D;.;.
Sift4G
Uncertain
0.037
D;D;D
Polyphen
1.0
D;D;D
Vest4
0.27
MutPred
0.27
Loss of methylation at R6 (P = 0.0211);Loss of methylation at R6 (P = 0.0211);Loss of methylation at R6 (P = 0.0211);
MVP
0.35
MPC
0.52
ClinPred
0.75
D
GERP RS
3.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.9
Varity_R
0.30
gMVP
0.31

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs2074236321; hg19: chr19-50354601; API