chr19-49858944-T-A

Position:

• chr19-49858944-T-A

Variant summary

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

The ENST00000391842.6(PTOV1):​c.1041+291T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.375 in 305,792 control chromosomes in the GnomAD database, including 22,342 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 0.39 (11876 hom., cov: 33)
  • Exomes 𝑓: 0.36 (10466 hom.)
• Consequence: PTOV1 ENST00000391842.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.46

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-AS2 (HGNC:51284): (PTOV1 antisense RNA 2)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.476 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTOV1	NM_001394010.1	c.1041+291T>A		intron_variant		ENST00000391842.6	NP_001380939.1
PTOV1-AS2	NR_110730.1	n.238A>T		non_coding_transcript_exon_variant	2/5
PTOV1	NR_130963.2	n.1116+291T>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTOV1	ENST00000391842.6	c.1041+291T>A		intron_variant		5	NM_001394010.1	ENSP00000375717	P1
PTOV1-AS2	ENST00000593654.1	n.238A>T		non_coding_transcript_exon_variant	2/5	2

Frequencies

GnomAD3 genomes AF: 0.387 AC: 58745 AN: 151946 Hom.: 11852 Cov.: 33

Gnomad AFR AF: 0.482

Gnomad AMI AF: 0.310

Gnomad AMR AF: 0.370

Gnomad ASJ AF: 0.431

Gnomad EAS AF: 0.427

Gnomad SAS AF: 0.493

Gnomad FIN AF: 0.226

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.346

Gnomad OTH AF: 0.378

GnomAD4 exome AF: 0.363 AC: 55875 AN: 153728 Hom.: 10466 Cov.: 0 AF XY: 0.366 AC XY: 28817 AN XY: 78668

Gnomad4 AFR exome AF: 0.477

Gnomad4 AMR exome AF: 0.341

Gnomad4 ASJ exome AF: 0.431

Gnomad4 EAS exome AF: 0.402

Gnomad4 SAS exome AF: 0.476

Gnomad4 FIN exome AF: 0.240

Gnomad4 NFE exome AF: 0.351

Gnomad4 OTH exome AF: 0.382

GnomAD4 genome AF: 0.387 AC: 58812 AN: 152064 Hom.: 11876 Cov.: 33 AF XY: 0.384 AC XY: 28552 AN XY: 74324

Gnomad4 AFR AF: 0.482

Gnomad4 AMR AF: 0.370

Gnomad4 ASJ AF: 0.431

Gnomad4 EAS AF: 0.427

Gnomad4 SAS AF: 0.493

Gnomad4 FIN AF: 0.226

Gnomad4 NFE AF: 0.346

Gnomad4 OTH AF: 0.383

Alfa AF: 0.345 Hom.: 1176

Bravo AF: 0.396

Asia WGS AF: 0.469 AC: 1630 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.37
DANN	Benign	0.85

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs7257463; hg19: chr19-50362201;