chr19-49856127-A-T

Position:

• chr19-49856127-A-T

Variant summary

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

The NM_001364747.2(PTOV1):​c.604-848A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 152,228 control chromosomes in the GnomAD database, including 1,408 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 0.12 (1408 hom., cov: 32)
  • Exomes 𝑓: 0.17 (0 hom.)
• Consequence: PTOV1 NM_001364747.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.421

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.189 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTOV1	NM_001364747.2	c.604-848A>T		intron_variant			NP_001351676.1
PTOV1	NM_001364749.2	c.604-848A>T		intron_variant			NP_001351678.1
PTOV1	NM_001305105.2	c.559-848A>T		intron_variant			NP_001292034.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTOV1	ENST00000391842.6	c.559-848A>T		intron_variant		5		ENSP00000375717.1

Frequencies

GnomAD3 genomes AF: 0.121 AC: 18336 AN: 152056 Hom.: 1407 Cov.: 32

Gnomad AFR AF: 0.0318

Gnomad AMI AF: 0.159

Gnomad AMR AF: 0.120

Gnomad ASJ AF: 0.238

Gnomad EAS AF: 0.0730

Gnomad SAS AF: 0.201

Gnomad FIN AF: 0.163

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.159

Gnomad OTH AF: 0.132

GnomAD4 exome AF: 0.167 AC: 9 AN: 54 Hom.: 0 Cov.: 0 AF XY: 0.190 AC XY: 8 AN XY: 42

Gnomad4 FIN exome AF: 0.125

Gnomad4 NFE exome AF: 0.174

GnomAD4 genome AF: 0.120 AC: 18334 AN: 152174 Hom.: 1408 Cov.: 32 AF XY: 0.122 AC XY: 9059 AN XY: 74390

Gnomad4 AFR AF: 0.0318

Gnomad4 AMR AF: 0.121

Gnomad4 ASJ AF: 0.238

Gnomad4 EAS AF: 0.0730

Gnomad4 SAS AF: 0.200

Gnomad4 FIN AF: 0.163

Gnomad4 NFE AF: 0.159

Gnomad4 OTH AF: 0.131

Alfa AF: 0.136 Hom.: 200

Bravo AF: 0.110

Asia WGS AF: 0.127 AC: 441 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.81
DANN	Benign	0.70

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: rs3786662; hg19: chr19-50359384;