chr19-49851444-C-T

Variant names:

• chr19-49851444-C-T
• rs542896699
• NM_001394010.1:c.116C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001394010.1(PTOV1):​c.116C>T​(p.Ala39Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000123 in 1,220,022 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000094 (0 hom.)
• Consequence: PTOV1 NM_001394010.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.116
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.008295506).

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.116C>T	p.Ala39Val	missense	Exon 1 of 12	NP_001380939.1	Q86YD1-1
	PTOV1	NM_001305105.2		c.116C>T	p.Ala39Val	missense	Exon 1 of 13	NP_001292034.1	Q86YD1-1
	PTOV1	NM_017432.5		c.116C>T	p.Ala39Val	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.116C>T	p.Ala39Val	missense	Exon 1 of 12	ENSP00000375717.1	Q86YD1-1
	PTOV1	ENST00000599732.5	TSL:1	c.116C>T	p.Ala39Val	missense	Exon 1 of 13	ENSP00000469128.1	Q86YD1-1
	PTOV1	ENST00000601675.5	TSL:1	c.116C>T	p.Ala39Val	missense	Exon 1 of 13	ENSP00000472816.1	Q86YD1-1

Frequencies

GnomAD3 genomes AF: 0.0000331 AC: 5 AN: 151188 Hom.: 0 Cov.: 32

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: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000443

Gnomad OTH AF: 0.000482

GnomAD2 exomes AF: 0.00225 AC: 1 AN: 444 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00427

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000936 AC: 10 AN: 1068834 Hom.: 0 Cov.: 31 AF XY: 0.0000139 AC XY: 7 AN XY: 505192

African (AFR) AF: 0.00 AC: 0 AN: 22358

American (AMR) AF: 0.000124 AC: 1 AN: 8034

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13734

East Asian (EAS) AF: 0.00 AC: 0 AN: 25724

South Asian (SAS) AF: 0.0000510 AC: 1 AN: 19612

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 20796

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2854

European-Non Finnish (NFE) AF: 0.00000767 AC: 7 AN: 912996

Other (OTH) AF: 0.0000234 AC: 1 AN: 42726

GnomAD4 genome AF: 0.0000331 AC: 5 AN: 151188 Hom.: 0 Cov.: 32 AF XY: 0.0000271 AC XY: 2 AN XY: 73822

African (AFR) AF: 0.00 AC: 0 AN: 41244

American (AMR) AF: 0.00 AC: 0 AN: 15196

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3454

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10348

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

European-Non Finnish (NFE) AF: 0.0000443 AC: 3 AN: 67656

Other (OTH) AF: 0.000482 AC: 1 AN: 2076

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000264

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.016	T
Eigen	Benign	-0.75
Eigen_PC	Benign	-0.74
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.39	T
M_CAP	Pathogenic	0.47	D
MetaRNN	Benign	0.0083	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.12
PrimateAI	Pathogenic	0.91	D
PROVEAN	Benign	0.29	N
REVEL	Benign	0.024
Sift	Benign	0.088	T
Sift4G	Benign	0.18	T
Polyphen		0.33	B
Vest4		0.16
MutPred		0.17		Loss of relative solvent accessibility (P = 0.0071)
MVP		0.048
MPC		0.16
ClinPred		0.057	T
GERP RS		1.3
PromoterAI		-0.11	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3
Varity_R		0.034
gMVP		0.14
Mutation Taster		=98/2	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: rs542896699; hg19: chr19-50354701;