Variant 19-49854448-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000391842.6(PTOV1):c.214T>G(p.Ser72Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PTOV1
ENST00000391842.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.480

Variant links:

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 links:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

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=0.1725901).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTOV1	NM_001394010.1 linkuse as main transcript	c.214T>G	p.Ser72Ala	missense_variant	2/12	ENST00000391842.6
PTOV1	NR_130963.2 linkuse as main transcript	n.294T>G		non_coding_transcript_exon_variant	2/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTOV1	ENST00000391842.6 linkuse as main transcript	c.214T>G	p.Ser72Ala	missense_variant	2/12	5	NM_001394010.1	P1	Q86YD1-1
	ENST00000601211.1 linkuse as main transcript	n.161+7A>C		splice_region_variant, intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

6.85e-7

AC:

AN:

1459916

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726300

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 17, 2023

The c.214T>G (p.S72A) alteration is located in exon 2 (coding exon 2) of the PTOV1 gene. This alteration results from a T to G substitution at nucleotide position 214, causing the serine (S) at amino acid position 72 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.069

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.011

T;.;.;T;T;T;T

Eigen

Benign

-0.18

Eigen_PC

Benign

-0.066

FATHMM_MKL

Uncertain

0.83

LIST_S2

Benign

0.50

T;T;T;T;.;.;T

M_CAP

Benign

0.029

MetaRNN

Benign

0.17

T;T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

.;.;.;N;N;N;.

MutationTaster

Benign

0.97

N;N

PrimateAI

Uncertain

0.65

PROVEAN

Benign

-1.0

.;.;.;N;.;.;.

REVEL

Benign

0.21

Sift

Benign

0.24

.;.;.;T;.;.;.

Sift4G

Benign

0.29

T;T;T;T;T;T;T

Polyphen

0.0070

.;.;.;B;B;B;.

Vest4

0.47, 0.46, 0.40, 0.41, 0.41

MutPred

0.14

.;.;.;Loss of glycosylation at S72 (P = 0.0118);Loss of glycosylation at S72 (P = 0.0118);Loss of glycosylation at S72 (P = 0.0118);.;

MVP

0.79

MPC

0.13

ClinPred

0.30

GERP RS

3.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.083

gMVP

0.19

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over