19-49851350-C-G

Variant names:

• chr19-49851350-C-G
• ENST00000391842.6:c.22C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_017432.5(PTOV1):​c.22C>G​(p.Pro8Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000105 in 949,932 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000011 (0 hom.)
• Consequence: PTOV1 NM_017432.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.06

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14660683).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTOV1	NM_001305105.2	c.22C>G	p.Pro8Ala	missense_variant	Exon 1 of 13		NP_001292034.1
PTOV1	NM_001394010.1	c.22C>G	p.Pro8Ala	missense_variant	Exon 1 of 12		NP_001380939.1
PTOV1	NM_017432.5	c.22C>G	p.Pro8Ala	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.22C>G	p.Pro8Ala	missense_variant	Exon 1 of 12	5		ENSP00000375717.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000105 AC: 1 AN: 949932 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 446146

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000226

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	22
DANN	Benign	0.97
DEOGEN2	Benign	0.019	T;T;T
Eigen	Benign	-0.46
Eigen_PC	Benign	-0.34
FATHMM_MKL	Benign	0.58	D
LIST_S2	Benign	0.54	T;.;.
M_CAP	Pathogenic	0.52	D
MetaRNN	Benign	0.15	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N;N;N
PrimateAI	Pathogenic	0.91	D
PROVEAN	Benign	-0.62	N;.;.
REVEL	Benign	0.062
Sift	Benign	0.24	T;.;.
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		0.015	B;B;B
Vest4		0.11
MutPred		0.18		Gain of helix (P = 0.0093);Gain of helix (P = 0.0093);Gain of helix (P = 0.0093);
MVP		0.22
MPC		0.40
ClinPred		0.17	T
GERP RS		3.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3
Varity_R		0.088
gMVP		0.13

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: chr19-50354607;