rs202190749

Variant names:

• chr19-49854722-A-C
• rs202190749
• ENST00000391842.6:c.380A>C

Your query was ambiguous. Multiple possible variants found:

• chr19-49854722-A-C
• chr19-49854722-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001364747.2(PTOV1):​c.425A>C​(p.Gln142Pro) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PTOV1 NM_001364747.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0970

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]

ENSG00000268047 (HGNC:):

MIR4749 (HGNC:41760): (microRNA 4749) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ACMG classification

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=0.07497129).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTOV1	NM_001364747.2	c.425A>C	p.Gln142Pro	missense_variant	Exon 3 of 13		NP_001351676.1
PTOV1	NM_001364749.2	c.425A>C	p.Gln142Pro	missense_variant	Exon 3 of 13		NP_001351678.1
PTOV1	NM_001305105.2	c.380A>C	p.Gln127Pro	missense_variant	Exon 3 of 13		NP_001292034.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTOV1	ENST00000391842.6	c.380A>C	p.Gln127Pro	missense_variant	Exon 3 of 12	5		ENSP00000375717.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.046	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	18
DANN	Benign	0.90
DEOGEN2	Benign	0.014	T;.;.;T;T;T;T
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.39	N
LIST_S2	Benign	0.79	T;T;T;T;.;.;T
M_CAP	Uncertain	0.19	D
MetaRNN	Benign	0.075	T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.3	.;.;.;L;L;L;.
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-2.0	.;.;.;N;.;.;.
REVEL	Benign	0.034
Sift	Benign	0.42	.;.;.;T;.;.;.
Sift4G	Benign	0.27	T;T;T;T;T;T;T
Polyphen		0.0	.;.;.;B;B;B;.
Vest4		0.37, 0.36, 0.32, 0.32, 0.32
MutPred		0.34		.;.;.;Loss of sheet (P = 0.0457);Loss of sheet (P = 0.0457);Loss of sheet (P = 0.0457);.;
MVP		0.48
MPC		0.13
ClinPred		0.093	T
GERP RS		-0.21
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.23
gMVP		0.87

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

LitVar

Other links and lift over

dbSNP: rs202190749; hg19: chr19-50357979;