19-49851344-C-A

Variant names:

• chr19-49851344-C-A
• rs2074236321
• NM_001394010.1:c.16C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001394010.1(PTOV1):​c.16C>A​(p.Arg6Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000193 in 1,088,998 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R6C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000068 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000021 (0 hom.)
• Consequence: PTOV1 NM_001394010.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.668
• Publications: 0 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]

PTOV1-AS1 (HGNC:44174): (PTOV1 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2067101).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTOV1	NM_001394010.1	MANE Select	c.16C>A	p.Arg6Ser	missense	Exon 1 of 12	NP_001380939.1	Q86YD1-1
	PTOV1	NM_001305105.2		c.16C>A	p.Arg6Ser	missense	Exon 1 of 13	NP_001292034.1	Q86YD1-1
	PTOV1	NM_017432.5		c.16C>A	p.Arg6Ser	missense	Exon 1 of 13	NP_059128.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTOV1	ENST00000391842.6	TSL:5 MANE Select	c.16C>A	p.Arg6Ser	missense	Exon 1 of 12	ENSP00000375717.1	Q86YD1-1
	PTOV1	ENST00000599732.5	TSL:1	c.16C>A	p.Arg6Ser	missense	Exon 1 of 13	ENSP00000469128.1	Q86YD1-1
	PTOV1	ENST00000601675.5	TSL:1	c.16C>A	p.Arg6Ser	missense	Exon 1 of 13	ENSP00000472816.1	Q86YD1-1

Frequencies

GnomAD3 genomes AF: 0.00000676 AC: 1 AN: 147986 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000151

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000213 AC: 20 AN: 941012 Hom.: 0 Cov.: 32 AF XY: 0.0000226 AC XY: 10 AN XY: 441610

African (AFR) AF: 0.00 AC: 0 AN: 18426

American (AMR) AF: 0.00 AC: 0 AN: 4172

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 8562

East Asian (EAS) AF: 0.00 AC: 0 AN: 11422

South Asian (SAS) AF: 0.00 AC: 0 AN: 18310

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 11352

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2170

European-Non Finnish (NFE) AF: 0.0000240 AC: 20 AN: 832516

Other (OTH) AF: 0.00 AC: 0 AN: 34082

GnomAD4 genome AF: 0.00000676 AC: 1 AN: 147986 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 72118

African (AFR) AF: 0.00 AC: 0 AN: 40742

American (AMR) AF: 0.00 AC: 0 AN: 14954

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3410

East Asian (EAS) AF: 0.00 AC: 0 AN: 5092

South Asian (SAS) AF: 0.00 AC: 0 AN: 4764

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9436

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000151 AC: 1 AN: 66342

Other (OTH) AF: 0.00 AC: 0 AN: 2036

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.77
BayesDel_addAF	Uncertain	0.018	T
BayesDel_noAF	Benign	-0.21
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.017	T
Eigen	Benign	-0.045
Eigen_PC	Benign	-0.051
FATHMM_MKL	Benign	0.59	D
LIST_S2	Benign	0.54	T
M_CAP	Pathogenic	0.56	D
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.67
PrimateAI	Pathogenic	0.94	D
PROVEAN	Benign	-0.080	N
REVEL	Benign	0.15
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.15	T
Polyphen		0.96	D
Vest4		0.27
MutPred		0.22		Gain of phosphorylation at R6 (P = 0.0042)
MVP		0.37
MPC		0.39
ClinPred		0.62	D
GERP RS		3.5
PromoterAI		-0.11	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.9
Varity_R		0.33
gMVP		0.39
Mutation Taster		=89/11	polymorphism

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: rs2074236321; hg19: chr19-50354601;