chr19-49851351-C-T

Position:

• chr19-49851351-C-T

Variant summary

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

The ENST00000391842.6(PTOV1):​c.23C>T​(p.Pro8Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000105 in 950,978 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. P8S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000011 (0 hom.)
• Consequence: PTOV1 ENST00000391842.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.00400

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

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=0.11430055).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTOV1	NM_001394010.1	c.23C>T	p.Pro8Leu	missense_variant	1/12	ENST00000391842.6
PTOV1-AS1	NR_040037.1	n.109+217G>A		intron_variant, non_coding_transcript_variant
PTOV1	NR_130963.2	n.251+396C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTOV1	ENST00000391842.6	c.23C>T	p.Pro8Leu	missense_variant	1/12	5	NM_001394010.1	P1
PTOV1-AS1	ENST00000596521.1	n.109+217G>A		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000105 AC: 1 AN: 950978 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 446590

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: 0.00000119

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

May 13, 2024

The c.23C>T (p.P8L) 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 23, causing the proline (P) at amino acid position 8 to be replaced by a leucine (L). 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	0.44
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.028	T;T;T
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.62
FATHMM_MKL	Benign	0.30	N
LIST_S2	Benign	0.58	T;.;.
M_CAP	Pathogenic	0.61	D
MetaRNN	Benign	0.11	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N;N;N
MutationTaster	Benign	0.96	D;D
PrimateAI	Pathogenic	0.93	D
PROVEAN	Benign	-1.1	N;.;.
REVEL	Benign	0.023
Sift	Benign	1.0	T;.;.
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		0.0010	B;B;B
Vest4		0.14
MutPred		0.22		Loss of loop (P = 0.0112);Loss of loop (P = 0.0112);Loss of loop (P = 0.0112);
MVP		0.17
MPC		0.47
ClinPred		0.73	D
GERP RS		1.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3
Varity_R		0.069
gMVP		0.15

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: chr19-50354608;