rs1290646

Positions:

• chr19-49859918-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000391842.6(PTOV1):​c.1042-68A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.537 in 1,542,698 control chromosomes in the GnomAD database, including 228,294 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.61 (30105 hom., cov: 34)
  • Exomes 𝑓: 0.53 (198189 hom.)
• Consequence: PTOV1 ENST00000391842.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.886

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]

PNKP (HGNC:9154): (polynucleotide kinase 3'-phosphatase) This locus represents a gene involved in DNA repair. In response to ionizing radiation or oxidative damage, the protein encoded by this locus catalyzes 5' phosphorylation and 3' dephosphorylation of nucleic acids. Mutations at this locus have been associated with microcephaly, seizures, and developmental delay.[provided by RefSeq, Sep 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.822 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTOV1	NM_001394010.1	c.1042-68A>G		intron_variant		ENST00000391842.6
PTOV1	NR_130963.2	n.1117-68A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTOV1	ENST00000391842.6	c.1042-68A>G		intron_variant		5	NM_001394010.1	P1

Frequencies

GnomAD3 genomes AF: 0.613 AC: 93188 AN: 152076 Hom.: 30056 Cov.: 34

Gnomad AFR AF: 0.829

Gnomad AMI AF: 0.735

Gnomad AMR AF: 0.527

Gnomad ASJ AF: 0.652

Gnomad EAS AF: 0.528

Gnomad SAS AF: 0.661

Gnomad FIN AF: 0.551

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.510

Gnomad OTH AF: 0.599

GnomAD4 exome AF: 0.529 AC: 735135 AN: 1390504 Hom.: 198189 Cov.: 23 AF XY: 0.534 AC XY: 371095 AN XY: 695008

Gnomad4 AFR exome AF: 0.837

Gnomad4 AMR exome AF: 0.454

Gnomad4 ASJ exome AF: 0.651

Gnomad4 EAS exome AF: 0.506

Gnomad4 SAS exome AF: 0.664

Gnomad4 FIN exome AF: 0.548

Gnomad4 NFE exome AF: 0.506

Gnomad4 OTH exome AF: 0.558

GnomAD4 genome AF: 0.613 AC: 93290 AN: 152194 Hom.: 30105 Cov.: 34 AF XY: 0.615 AC XY: 45765 AN XY: 74386

Gnomad4 AFR AF: 0.829

Gnomad4 AMR AF: 0.527

Gnomad4 ASJ AF: 0.652

Gnomad4 EAS AF: 0.528

Gnomad4 SAS AF: 0.659

Gnomad4 FIN AF: 0.551

Gnomad4 NFE AF: 0.510

Gnomad4 OTH AF: 0.602

Alfa AF: 0.534 Hom.: 27582

Bravo AF: 0.616

Asia WGS AF: 0.613 AC: 2133 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.97
DANN	Benign	0.56

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: rs1290646; hg19: chr19-50363175; COSMIC: COSV55586150; COSMIC: COSV55586150;