19-49851429-C-T

Variant names:

• chr19-49851429-C-T
• rs1411674780
• NM_001394010.1:c.101C>T

Variant summary

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

The NM_001394010.1(PTOV1):​c.101C>T​(p.Ser34Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000247 in 1,215,302 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 9.4e-7 (0 hom.)
• Consequence: PTOV1 NM_001394010.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.23
• 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=0.30087236).

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.101C>T	p.Ser34Leu	missense	Exon 1 of 12	NP_001380939.1	Q86YD1-1
	PTOV1	NM_001305105.2		c.101C>T	p.Ser34Leu	missense	Exon 1 of 13	NP_001292034.1	Q86YD1-1
	PTOV1	NM_017432.5		c.101C>T	p.Ser34Leu	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.101C>T	p.Ser34Leu	missense	Exon 1 of 12	ENSP00000375717.1	Q86YD1-1
	PTOV1	ENST00000599732.5	TSL:1	c.101C>T	p.Ser34Leu	missense	Exon 1 of 13	ENSP00000469128.1	Q86YD1-1
	PTOV1	ENST00000601675.5	TSL:1	c.101C>T	p.Ser34Leu	missense	Exon 1 of 13	ENSP00000472816.1	Q86YD1-1

Frequencies

GnomAD3 genomes AF: 0.0000133 AC: 2 AN: 150822 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000243

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000660

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: 0.00

GnomAD4 exome AF: 9.39e-7 AC: 1 AN: 1064480 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 503344

African (AFR) AF: 0.00 AC: 0 AN: 22208

American (AMR) AF: 0.00 AC: 0 AN: 7878

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13488

East Asian (EAS) AF: 0.00 AC: 0 AN: 25248

South Asian (SAS) AF: 0.00 AC: 0 AN: 19648

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 20616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2820

European-Non Finnish (NFE) AF: 0.00000110 AC: 1 AN: 910212

Other (OTH) AF: 0.00 AC: 0 AN: 42362

GnomAD4 genome AF: 0.0000133 AC: 2 AN: 150822 Hom.: 0 Cov.: 32 AF XY: 0.0000136 AC XY: 1 AN XY: 73606

African (AFR) AF: 0.0000243 AC: 1 AN: 41196

American (AMR) AF: 0.0000660 AC: 1 AN: 15158

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3450

East Asian (EAS) AF: 0.00 AC: 0 AN: 5148

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10232

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67524

Other (OTH) AF: 0.00 AC: 0 AN: 2072

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.41
BayesDel_addAF	Benign	-0.030	T
BayesDel_noAF	Benign	-0.28
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.026	T
Eigen	Benign	0.14
Eigen_PC	Benign	0.17
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.68	T
M_CAP	Pathogenic	0.79	D
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	0.0	N
PhyloP100		1.2
PrimateAI	Pathogenic	0.93	D
PROVEAN	Benign	-1.1	N
REVEL	Uncertain	0.38
Sift	Uncertain	0.023	D
Sift4G	Benign	0.11	T
Polyphen		0.98	D
Vest4		0.39
MutPred		0.24		Loss of phosphorylation at S34 (P = 0.0053)
MVP		0.35
MPC		0.11
ClinPred		0.61	D
GERP RS		3.5
PromoterAI		-0.016	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.9
Varity_R		0.15
gMVP		0.17
Mutation Taster		=97/3	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: rs1411674780; hg19: chr19-50354686;