rs1290646

Variant names:

• chr19-49859918-A-G
• rs1290646
• NM_001394010.1:c.1042-68A>G

Your query was ambiguous. Multiple possible variants found:

• chr19-49859918-A-G
• chr19-49859918-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001394010.1(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 NM_001394010.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.886
• Publications: 18 publications found

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]

PNKP Gene-Disease associations (from GenCC):

• ataxia - oculomotor apraxia type 4

  Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, G2P, Laboratory for Molecular Medicine
• microcephaly, seizures, and developmental delay

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• Charcot-Marie-Tooth disease type 2B2

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)
• genetic developmental and epileptic encephalopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001394010.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTOV1	NM_001394010.1	MANE Select	c.1042-68A>G		intron	N/A	NP_001380939.1
	PTOV1	NM_001364747.2		c.1087-68A>G		intron	N/A	NP_001351676.1
	PTOV1	NM_001364749.2		c.1087-68A>G		intron	N/A	NP_001351678.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTOV1	ENST00000391842.6	TSL:5 MANE Select	c.1042-68A>G		intron	N/A	ENSP00000375717.1
	PTOV1	ENST00000599732.5	TSL:1	c.1042-68A>G		intron	N/A	ENSP00000469128.1
	PTOV1	ENST00000601675.5	TSL:1	c.1042-68A>G		intron	N/A	ENSP00000472816.1

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

African (AFR) AF: 0.837 AC: 26735 AN: 31942

American (AMR) AF: 0.454 AC: 20117 AN: 44292

Ashkenazi Jewish (ASJ) AF: 0.651 AC: 16533 AN: 25412

East Asian (EAS) AF: 0.506 AC: 19846 AN: 39238

South Asian (SAS) AF: 0.664 AC: 56007 AN: 84392

European-Finnish (FIN) AF: 0.548 AC: 28795 AN: 52506

Middle Eastern (MID) AF: 0.672 AC: 3736 AN: 5562

European-Non Finnish (NFE) AF: 0.506 AC: 531049 AN: 1049230

Other (OTH) AF: 0.558 AC: 32317 AN: 57930

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

African (AFR) AF: 0.829 AC: 34464 AN: 41554

American (AMR) AF: 0.527 AC: 8058 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.652 AC: 2264 AN: 3472

East Asian (EAS) AF: 0.528 AC: 2725 AN: 5160

South Asian (SAS) AF: 0.659 AC: 3185 AN: 4830

European-Finnish (FIN) AF: 0.551 AC: 5836 AN: 10592

Middle Eastern (MID) AF: 0.578 AC: 170 AN: 294

European-Non Finnish (NFE) AF: 0.510 AC: 34646 AN: 67968

Other (OTH) AF: 0.602 AC: 1272 AN: 2112

Alfa AF: 0.554 Hom.: 56672

Bravo AF: 0.616

Asia WGS AF: 0.613 AC: 2133 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.97
DANN	Benign	0.56
PhyloP100		-0.89
PromoterAI		-0.021	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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