rs372052304

Variant names:

• chr19-49860017-C-G
• ENST00000391842.6:c.1073C>G

Your query was ambiguous. Multiple possible variants found:

• chr19-49860017-C-G
• chr19-49860017-C-T

Variant summary

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

The NM_001364747.2(PTOV1):​c.1118C>G​(p.Ser373Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,842 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: PTOV1 NM_001364747.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.03

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]

PNKP (HGNC:9154): (polynucleotide kinase 3'-phosphatase) This locus represents a gene involved in DNA repair. In response to ionizing radiation or oxidative damage, the protein encoded by this locus catalyzes 5' phosphorylation and 3' dephosphorylation of nucleic acids. Mutations at this locus have been associated with microcephaly, seizures, and developmental delay.[provided by RefSeq, Sep 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTOV1	NM_001364747.2	c.1118C>G	p.Ser373Trp	missense_variant	Exon 11 of 13		NP_001351676.1
PTOV1	NM_001364749.2	c.1118C>G	p.Ser373Trp	missense_variant	Exon 11 of 13		NP_001351678.1
PTOV1	NM_001305105.2	c.1073C>G	p.Ser358Trp	missense_variant	Exon 11 of 13		NP_001292034.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTOV1	ENST00000391842.6	c.1073C>G	p.Ser358Trp	missense_variant	Exon 11 of 12	5		ENSP00000375717.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461842 Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1 AN XY: 727222

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.45
BayesDel_addAF	Benign	-0.0068	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.20	.;T;T;T
Eigen	Benign	0.049
Eigen_PC	Benign	-0.051
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.79	T;T;.;.
M_CAP	Benign	0.043	D
MetaRNN	Uncertain	0.58	D;D;D;D
MetaSVM	Benign	-0.55	T
MutationAssessor	Benign	0.0	.;N;N;N
PrimateAI	Benign	0.38	T
PROVEAN	Uncertain	-3.4	.;D;.;.
REVEL	Uncertain	0.41
Sift	Uncertain	0.018	.;D;.;.
Sift4G	Uncertain	0.0030	D;D;D;D
Polyphen		1.0	.;D;D;D
Vest4		0.59
MutPred		0.47		.;Loss of relative solvent accessibility (P = 0.0793);Loss of relative solvent accessibility (P = 0.0793);Loss of relative solvent accessibility (P = 0.0793);
MVP		0.30
MPC		0.27
ClinPred		0.94	D
GERP RS		4.3
Varity_R		0.30
gMVP		0.29

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-50363274;