dbSNP rs1290646: PTOV1:c.1042-68A>G (chr19-49859918-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.886

Variant links:

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 links:

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]

PNKP links:

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ACMG classification

Classification made for transcript

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	Effect	Exon rank	Protein	UniProt
PTOV1	NM_001364747.2 link	c.1087-68A>G	intron_variant	Intron 10 of 12	NP_001351676.1
PTOV1	NM_001364749.2 link	c.1087-68A>G	intron_variant	Intron 10 of 12	NP_001351678.1
PTOV1	NM_001305105.2 link	c.1042-68A>G	intron_variant	Intron 10 of 12	NP_001292034.1	Q86YD1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTOV1	ENST00000391842.6 link	c.1042-68A>G		intron_variant	Intron 10 of 11	5		ENSP00000375717.1		Q86YD1-1

Frequencies

GnomAD3 genomes

AF:

0.613

AC:

93188

AN:

152076

Hom.:

30056

Cov.:

show subpopulations

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.:

AF XY:

0.534

AC XY:

371095

AN XY:

695008

show subpopulations

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.:

AF XY:

0.615

AC XY:

45765

AN XY:

74386

show subpopulations

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over