chr19-49851366-C-A

Variant names:

• chr19-49851366-C-A
• rs575608015
• NM_001394010.1:c.38C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001394010.1(PTOV1):​c.38C>A​(p.Ala13Asp) 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A13V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PTOV1 NM_001394010.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.280
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.095924854).

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.38C>A	p.Ala13Asp	missense	Exon 1 of 12	NP_001380939.1	Q86YD1-1
	PTOV1	NM_001305105.2		c.38C>A	p.Ala13Asp	missense	Exon 1 of 13	NP_001292034.1	Q86YD1-1
	PTOV1	NM_017432.5		c.38C>A	p.Ala13Asp	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.38C>A	p.Ala13Asp	missense	Exon 1 of 12	ENSP00000375717.1	Q86YD1-1
	PTOV1	ENST00000599732.5	TSL:1	c.38C>A	p.Ala13Asp	missense	Exon 1 of 13	ENSP00000469128.1	Q86YD1-1
	PTOV1	ENST00000601675.5	TSL:1	c.38C>A	p.Ala13Asp	missense	Exon 1 of 13	ENSP00000472816.1	Q86YD1-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

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	Benign	0.27
BayesDel_addAF	Benign	-0.086	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	21
DANN	Benign	0.97
DEOGEN2	Benign	0.020	T
Eigen	Benign	-0.84
Eigen_PC	Benign	-0.85
FATHMM_MKL	Benign	0.099	N
LIST_S2	Benign	0.49	T
M_CAP	Pathogenic	0.46	D
MetaRNN	Benign	0.096	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.28
PrimateAI	Pathogenic	0.90	D
PROVEAN	Benign	-0.79	N
REVEL	Benign	0.073
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.058	T
Polyphen		0.31	B
Vest4		0.24
MutPred		0.16		Loss of methylation at R10 (P = 0.0757)
MVP		0.088
MPC		0.15
ClinPred		0.26	T
GERP RS		-1.4
PromoterAI		-0.030	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.6
Varity_R		0.51
gMVP		0.29
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: rs575608015; hg19: chr19-50354623;