rs1379794257

Variant names:

• chr19-49851393-G-A
• rs1379794257
• ENST00000391842.6:c.65G>A

Your query was ambiguous. Multiple possible variants found:

• chr19-49851393-G-A
• chr19-49851393-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The ENST00000391842.6(PTOV1):​c.65G>A​(p.Arg22His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000017 in 1,174,120 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict 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. R22L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000068 (0 hom., cov: 32)
  • Exomes 𝑓: 9.7e-7 (0 hom.)
• Consequence: PTOV1 ENST00000391842.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.97
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3907362).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTOV1	NM_001305105.2	c.65G>A	p.Arg22His	missense_variant	Exon 1 of 13		NP_001292034.1
PTOV1	NM_001394010.1	c.65G>A	p.Arg22His	missense_variant	Exon 1 of 12		NP_001380939.1
PTOV1	NM_017432.5	c.65G>A	p.Arg22His	missense_variant	Exon 1 of 13		NP_059128.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTOV1	ENST00000391842.6	c.65G>A	p.Arg22His	missense_variant	Exon 1 of 12	5		ENSP00000375717.1

Frequencies

GnomAD3 genomes AF: 0.00000676 AC: 1 AN: 147906 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: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00325

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00 AC: 0 AN: 36 AF XY: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 9.75e-7 AC: 1 AN: 1026120 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 483920

African (AFR) AF: 0.0000478 AC: 1 AN: 20908

American (AMR) AF: 0.00 AC: 0 AN: 6572

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11802

East Asian (EAS) AF: 0.00 AC: 0 AN: 21642

South Asian (SAS) AF: 0.00 AC: 0 AN: 19092

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 18546

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2626

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 885392

Other (OTH) AF: 0.00 AC: 0 AN: 39540

GnomAD4 genome AF: 0.00000676 AC: 1 AN: 148000 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 72184

African (AFR) AF: 0.00 AC: 0 AN: 40402

American (AMR) AF: 0.00 AC: 0 AN: 14970

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3424

East Asian (EAS) AF: 0.00 AC: 0 AN: 5016

South Asian (SAS) AF: 0.00 AC: 0 AN: 4730

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9500

Middle Eastern (MID) AF: 0.00347 AC: 1 AN: 288

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 66698

Other (OTH) AF: 0.00 AC: 0 AN: 2076

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.075	T
BayesDel_noAF	Benign	-0.35
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.019	T;T;T
Eigen	Benign	0.091
Eigen_PC	Benign	0.050
FATHMM_MKL	Benign	0.52	D
LIST_S2	Benign	0.68	T;.;.
M_CAP	Pathogenic	0.71	D
MetaRNN	Benign	0.39	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N;N;N
PhyloP100		3.0
PrimateAI	Pathogenic	0.92	D
PROVEAN	Benign	-0.22	N;.;.
REVEL	Benign	0.27
Sift	Uncertain	0.015	D;.;.
Sift4G	Benign	0.15	T;T;T
Polyphen		0.99	D;D;D
Vest4		0.25
MutPred		0.26		Loss of methylation at R22 (P = 0.0109);Loss of methylation at R22 (P = 0.0109);Loss of methylation at R22 (P = 0.0109);
MVP		0.31
MPC		0.48
ClinPred		0.85	D
GERP RS		3.3
PromoterAI		-0.029	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.6
Varity_R		0.10
gMVP		0.29
Mutation Taster		=96/4	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: rs1379794257; hg19: chr19-50354650;