19-49854722-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000391842.6(PTOV1):c.380A>G(p.Gln127Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,461,240 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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: 0.0000062 (0 hom.)
• Consequence: PTOV1 ENST00000391842.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0970

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]

(HGNC:):

ACMG classification

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=0.16427818).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTOV1	NM_001394010.1	c.380A>G	p.Gln127Arg	missense_variant	3/12	ENST00000391842.6
PTOV1	NR_130963.2	n.460A>G		non_coding_transcript_exon_variant	3/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTOV1	ENST00000391842.6	c.380A>G	p.Gln127Arg	missense_variant	3/12	5	NM_001394010.1	P1
	ENST00000601211.1	n.25-131T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000399 AC: 1 AN: 250770 Hom.: 0 AF XY: 0.00000737 AC XY: 1 AN XY: 135738

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000883

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000616 AC: 9 AN: 1461240 Hom.: 0 Cov.: 33 AF XY: 0.00000550 AC XY: 4 AN XY: 726968

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: 0.00000809

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 16, 2023

The c.380A>G (p.Q127R) alteration is located in exon 3 (coding exon 3) of the PTOV1 gene. This alteration results from a A to G substitution at nucleotide position 380, causing the glutamine (Q) at amino acid position 127 to be replaced by an arginine (R). 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	0.17
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
Cadd	Benign	20
Dann	Uncertain	0.99
DEOGEN2	Benign	0.027	T;.;.;T;T;T;T
Eigen	Benign	-0.15
Eigen_PC	Benign	-0.17
FATHMM_MKL	Benign	0.34	N
LIST_S2	Benign	0.70	T;T;T;T;.;.;T
M_CAP	Uncertain	0.16	D
MetaRNN	Benign	0.16	T;T;T;T;T;T;T
MetaSVM	Benign	-0.83	T
MutationTaster	Benign	0.77	D;D
PrimateAI	Uncertain	0.52	T
Sift4G	Benign	0.35	T;T;T;T;T;T;T
Polyphen		0.0	.;.;.;B;B;B;.
Vest4		0.26, 0.28, 0.29, 0.30, 0.29
MutPred		0.30		.;.;.;Gain of solvent accessibility (P = 0.0261);Gain of solvent accessibility (P = 0.0261);Gain of solvent accessibility (P = 0.0261);.;
MVP		0.70
MPC		0.11
ClinPred		0.63	D
GERP RS		-0.21
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.11
gMVP		0.58

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

Other links and lift over

dbSNP: rs202190749; hg19: chr19-50357979;