19-49851410-G-T

Variant names:

• chr19-49851410-G-T
• rs989773452
• NM_001394010.1:c.82G>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.82G>T​(p.Val28Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000334 in 1,198,420 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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. V28M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 9.5e-7 (0 hom.)
• Consequence: PTOV1 NM_001394010.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.342
• 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=0.05488187).

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.82G>T	p.Val28Leu	missense	Exon 1 of 12	NP_001380939.1	Q86YD1-1
	PTOV1	NM_001305105.2		c.82G>T	p.Val28Leu	missense	Exon 1 of 13	NP_001292034.1	Q86YD1-1
	PTOV1	NM_017432.5		c.82G>T	p.Val28Leu	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.82G>T	p.Val28Leu	missense	Exon 1 of 12	ENSP00000375717.1	Q86YD1-1
	PTOV1	ENST00000599732.5	TSL:1	c.82G>T	p.Val28Leu	missense	Exon 1 of 13	ENSP00000469128.1	Q86YD1-1
	PTOV1	ENST00000601675.5	TSL:1	c.82G>T	p.Val28Leu	missense	Exon 1 of 13	ENSP00000472816.1	Q86YD1-1

Frequencies

GnomAD3 genomes AF: 0.0000201 AC: 3 AN: 148934 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000134

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000488

GnomAD4 exome AF: 9.53e-7 AC: 1 AN: 1049486 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 495788

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 21672

American (AMR) AF: 0.00 AC: 0 AN: 7362

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12790

East Asian (EAS) AF: 0.00 AC: 0 AN: 23952

South Asian (SAS) AF: 0.00 AC: 0 AN: 19442

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 19912

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2746

European-Non Finnish (NFE) AF: 0.00000111 AC: 1 AN: 900414

Other (OTH) AF: 0.00 AC: 0 AN: 41196

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000201 AC: 3 AN: 148934 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 72570

African (AFR) AF: 0.00 AC: 0 AN: 40642

American (AMR) AF: 0.000134 AC: 2 AN: 14960

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3436

East Asian (EAS) AF: 0.00 AC: 0 AN: 5062

South Asian (SAS) AF: 0.00 AC: 0 AN: 4784

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9760

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 300

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67036

Other (OTH) AF: 0.000488 AC: 1 AN: 2050

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	7.4
DANN	Benign	0.89
DEOGEN2	Benign	0.019	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.42	T
M_CAP	Uncertain	0.16	D
MetaRNN	Benign	0.055	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.34
PrimateAI	Pathogenic	0.93	D
PROVEAN	Benign	-0.010	N
REVEL	Benign	0.0070
Sift	Benign	0.34	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.072
MutPred		0.24		Loss of sheet (P = 0.0228)
MVP		0.12
MPC		0.098
ClinPred		0.093	T
GERP RS		-1.9
PromoterAI		0.046	Neutral
Varity_R		0.032
gMVP		0.14
Mutation Taster		=100/0	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: rs989773452; hg19: chr19-50354667;