rs1452783050

Variant names:

• chr19-49851377-C-G
• rs1452783050
• ENST00000391842.6:c.49C>G

Your query was ambiguous. Multiple possible variants found:

• chr19-49851377-C-G
• chr19-49851377-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000391842.6(PTOV1):​c.49C>G​(p.Leu17Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000105 in 1,147,582 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 (★).

• Frequency:
  • Genomes: 𝑓 0.0000067 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000011 (0 hom.)
• Consequence: PTOV1 ENST00000391842.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.184
• Publications: 0 publications found

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)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24457374).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTOV1	NM_001305105.2	c.49C>G	p.Leu17Val	missense_variant	Exon 1 of 13		NP_001292034.1
PTOV1	NM_001394010.1	c.49C>G	p.Leu17Val	missense_variant	Exon 1 of 12		NP_001380939.1
PTOV1	NM_017432.5	c.49C>G	p.Leu17Val	missense_variant	Exon 1 of 13		NP_059128.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTOV1	ENST00000391842.6	c.49C>G	p.Leu17Val	missense_variant	Exon 1 of 12	5		ENSP00000375717.1

Frequencies

GnomAD3 genomes AF: 0.00000672 AC: 1 AN: 148910 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000150

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000110 AC: 11 AN: 998672 Hom.: 0 Cov.: 32 AF XY: 0.0000106 AC XY: 5 AN XY: 470154

African (AFR) AF: 0.00 AC: 0 AN: 19952

American (AMR) AF: 0.00 AC: 0 AN: 5732

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10692

East Asian (EAS) AF: 0.00 AC: 0 AN: 18464

South Asian (SAS) AF: 0.00 AC: 0 AN: 18822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 16566

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2468

European-Non Finnish (NFE) AF: 0.0000127 AC: 11 AN: 868264

Other (OTH) AF: 0.00 AC: 0 AN: 37712

GnomAD4 genome AF: 0.00000672 AC: 1 AN: 148910 Hom.: 0 Cov.: 32 AF XY: 0.0000138 AC XY: 1 AN XY: 72620

African (AFR) AF: 0.00 AC: 0 AN: 40958

American (AMR) AF: 0.00 AC: 0 AN: 15004

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3422

East Asian (EAS) AF: 0.00 AC: 0 AN: 5130

South Asian (SAS) AF: 0.00 AC: 0 AN: 4804

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9572

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.0000150 AC: 1 AN: 66754

Other (OTH) AF: 0.00 AC: 0 AN: 2050

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 08, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.49C>G (p.L17V) alteration is located in exon 1 (coding exon 1) of the PTOV1 gene. This alteration results from a C to G substitution at nucleotide position 49, causing the leucine (L) at amino acid position 17 to be replaced by a valine (V). 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	0.078
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	20
DANN	Benign	0.88
DEOGEN2	Benign	0.016	T;T;T
Eigen	Benign	-0.074
Eigen_PC	Benign	-0.045
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.52	T;.;.
M_CAP	Pathogenic	0.54	D
MetaRNN	Benign	0.24	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N;N;N
PhyloP100		-0.18
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	-0.20	N;.;.
REVEL	Benign	0.080
Sift	Pathogenic	0.0	D;.;.
Sift4G	Benign	0.20	T;T;T
Polyphen		0.88	P;P;P
Vest4		0.21
MutPred		0.18		Loss of catalytic residue at L17 (P = 0.2145);Loss of catalytic residue at L17 (P = 0.2145);Loss of catalytic residue at L17 (P = 0.2145);
MVP		0.37
MPC		0.33
ClinPred		0.39	T
GERP RS		3.5
PromoterAI		0.0083	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.9
Varity_R		0.30
gMVP		0.083
Mutation Taster		=90/10	polymorphism

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

Other links and lift over

dbSNP: rs1452783050; hg19: chr19-50354634;