chr19-49851444-C-G

Variant names:

• chr19-49851444-C-G
• rs542896699
• ENST00000391842.6:c.116C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000391842.6(PTOV1):​c.116C>G​(p.Ala39Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00135 in 1,220,128 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A39V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0066 (8 hom., cov: 32)
  • Exomes 𝑓: 0.00061 (7 hom.)
• Consequence: PTOV1 ENST00000391842.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.116
• 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0020639002).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00656 (993/151296) while in subpopulation AFR AF = 0.0219 (904/41362). AF 95% confidence interval is 0.0207. There are 8 homozygotes in GnomAd4. There are 480 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTOV1	NM_001305105.2	c.116C>G	p.Ala39Gly	missense_variant	Exon 1 of 13		NP_001292034.1
PTOV1	NM_001394010.1	c.116C>G	p.Ala39Gly	missense_variant	Exon 1 of 12		NP_001380939.1
PTOV1	NM_017432.5	c.116C>G	p.Ala39Gly	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.116C>G	p.Ala39Gly	missense_variant	Exon 1 of 12	5		ENSP00000375717.1

Frequencies

GnomAD3 genomes AF: 0.00657 AC: 994 AN: 151188 Hom.: 9 Cov.: 32

Gnomad AFR AF: 0.0219

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00401

Gnomad ASJ AF: 0.00116

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00819

GnomAD2 exomes AF: 0.00 AC: 0 AN: 444 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000610 AC: 652 AN: 1068832 Hom.: 7 Cov.: 31 AF XY: 0.000574 AC XY: 290 AN XY: 505192

African (AFR) AF: 0.0217 AC: 486 AN: 22356

American (AMR) AF: 0.00349 AC: 28 AN: 8034

Ashkenazi Jewish (ASJ) AF: 0.000947 AC: 13 AN: 13734

East Asian (EAS) AF: 0.00 AC: 0 AN: 25724

South Asian (SAS) AF: 0.00 AC: 0 AN: 19612

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 20796

Middle Eastern (MID) AF: 0.000701 AC: 2 AN: 2854

European-Non Finnish (NFE) AF: 0.0000350 AC: 32 AN: 912996

Other (OTH) AF: 0.00213 AC: 91 AN: 42726

GnomAD4 genome AF: 0.00656 AC: 993 AN: 151296 Hom.: 8 Cov.: 32 AF XY: 0.00649 AC XY: 480 AN XY: 73940

African (AFR) AF: 0.0219 AC: 904 AN: 41362

American (AMR) AF: 0.00401 AC: 61 AN: 15216

Ashkenazi Jewish (ASJ) AF: 0.00116 AC: 4 AN: 3454

East Asian (EAS) AF: 0.00 AC: 0 AN: 5152

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10348

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 67646

Other (OTH) AF: 0.00810 AC: 17 AN: 2098

Alfa AF: 0.0000700 Hom.: 0

Bravo AF: 0.00805

ExAC AF: 0.000319 AC: 9

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.66	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	21
DANN	Benign	0.97
DEOGEN2	Benign	0.016	T;T;T
Eigen	Benign	-0.93
Eigen_PC	Benign	-0.88
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.27	T;.;.
MetaRNN	Benign	0.0021	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N;N;N
PhyloP100		0.12
PrimateAI	Pathogenic	0.90	D
PROVEAN	Benign	0.080	N;.;.
REVEL	Benign	0.027
Sift	Benign	0.67	T;.;.
Sift4G	Benign	0.80	T;T;T
Polyphen		0.092	B;B;B
Vest4		0.10
MutPred		0.17		Gain of catalytic residue at A39 (P = 0.1366);Gain of catalytic residue at A39 (P = 0.1366);Gain of catalytic residue at A39 (P = 0.1366);
MVP		0.040
MPC		0.10
ClinPred		0.19	T
GERP RS		1.3
PromoterAI		-0.040	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3
Varity_R		0.035
gMVP		0.15
Mutation Taster		=99/1	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: rs542896699; hg19: chr19-50354701;