rs1290646

Positions:

• chr19-49859918-A-G

Variant summary

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

The NM_001364747.2(PTOV1):​c.1087-68A>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 NM_001364747.2 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]

PTOV1 (HGNC:):

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	Protein	UniProt
PTOV1	NM_001364747.2	c.1087-68A>G		intron_variant			NP_001351676.1
PTOV1	NM_001364749.2	c.1087-68A>G		intron_variant			NP_001351678.1
PTOV1	NM_001305105.2	c.1042-68A>G		intron_variant			NP_001292034.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTOV1	ENST00000391842.6	c.1042-68A>G		intron_variant		5		ENSP00000375717.1

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;