ENST00000391842.6:c.49C>T

Variant names:

• chr19-49851377-C-T
• ENST00000391842.6:c.49C>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The ENST00000391842.6(PTOV1):​c.49C>T​(p.Leu17Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000002 in 998,672 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 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. L17V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000020 (0 hom.)
• Consequence: PTOV1 ENST00000391842.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.184

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29291803).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTOV1	NM_001305105.2	c.49C>T	p.Leu17Phe	missense_variant	Exon 1 of 13		NP_001292034.1
PTOV1	NM_001394010.1	c.49C>T	p.Leu17Phe	missense_variant	Exon 1 of 12		NP_001380939.1
PTOV1	NM_017432.5	c.49C>T	p.Leu17Phe	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.49C>T	p.Leu17Phe	missense_variant	Exon 1 of 12	5		ENSP00000375717.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000200 AC: 2 AN: 998672 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 470154

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000174

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000115

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.016	T;T;T
Eigen	Benign	0.069
Eigen_PC	Benign	0.063
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.46	T;.;.
M_CAP	Pathogenic	0.55	D
MetaRNN	Benign	0.29	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N;N;N
PrimateAI	Pathogenic	0.90	D
PROVEAN	Benign	0.070	N;.;.
REVEL	Benign	0.10
Sift	Pathogenic	0.0	D;.;.
Sift4G	Benign	0.25	T;T;T
Polyphen		0.98	D;D;D
Vest4		0.24
MutPred		0.17		Gain of methylation at R22 (P = 0.2059);Gain of methylation at R22 (P = 0.2059);Gain of methylation at R22 (P = 0.2059);
MVP		0.49
MPC		0.46
ClinPred		0.53	D
GERP RS		3.5
Varity_R		0.25
gMVP		0.074

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-50354634;