Variant rs13226149 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000940.3(PON3):c.63C>T(p.Phe21=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.279 in 1,613,292 control chromosomes in the GnomAD database, including 65,269 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.30 ( 7172 hom., cov: 30)

Exomes 𝑓: 0.28 ( 58097 hom. )

Consequence

PON3
NM_000940.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.77

Variant links:

Genes affected

PON3 (HGNC:9206): (paraoxonase 3) This gene is a member of the paraoxonase family and lies in a cluster on chromosome 7 with the other two family members. The encoded protein is secreted into the bloodstream and associates with high-density lipoprotein (HDL). The protein also rapidly hydrolyzes lactones and can inhibit the oxidation of low-density lipoprotein (LDL), a function that is believed to slow the initiation and progression of atherosclerosis. Alternatively spliced variants which encode different protein isoforms have been described; however, only one has been fully characterized. [provided by RefSeq, Jul 2008]

PON3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 7-95396288-G-A is Benign according to our data. Variant chr7-95396288-G-A is described in ClinVar as [Benign]. Clinvar id is 1268453.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.77 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.367 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PON3	NM_000940.3 linkuse as main transcript	c.63C>T	p.Phe21=	synonymous_variant	1/9	ENST00000265627.10	NP_000931.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PON3	ENST00000265627.10 linkuse as main transcript	c.63C>T	p.Phe21=	synonymous_variant	1/9	1	NM_000940.3	ENSP00000265627	P1

Frequencies

GnomAD3 genomes

AF:

0.298

AC:

45165

AN:

151612

Hom.:

7158

Cov.:

show subpopulations

Gnomad AFR

AF:

0.341

Gnomad AMI

AF:

0.478

Gnomad AMR

AF:

0.238

Gnomad ASJ

AF:

0.193

Gnomad EAS

AF:

0.179

Gnomad SAS

AF:

0.381

Gnomad FIN

AF:

0.465

Gnomad MID

AF:

0.263

Gnomad NFE

AF:

0.267

Gnomad OTH

AF:

0.261

GnomAD3 exomes

AF:

0.287

AC:

71408

AN:

249158

Hom.:

11038

AF XY:

0.293

AC XY:

39504

AN XY:

134858

show subpopulations

Gnomad AFR exome

AF:

0.353

Gnomad AMR exome

AF:

0.219

Gnomad ASJ exome

AF:

0.185

Gnomad EAS exome

AF:

0.170

Gnomad SAS exome

AF:

0.388

Gnomad FIN exome

AF:

0.447

Gnomad NFE exome

AF:

0.268

Gnomad OTH exome

AF:

0.269

GnomAD4 exome

AF:

0.277

AC:

404529

AN:

1461562

Hom.:

58097

Cov.:

AF XY:

0.280

AC XY:

203898

AN XY:

727114

show subpopulations

Gnomad4 AFR exome

AF:

0.359

Gnomad4 AMR exome

AF:

0.222

Gnomad4 ASJ exome

AF:

0.187

Gnomad4 EAS exome

AF:

0.195

Gnomad4 SAS exome

AF:

0.388

Gnomad4 FIN exome

AF:

0.440

Gnomad4 NFE exome

AF:

0.265

Gnomad4 OTH exome

AF:

0.275

GnomAD4 genome

AF:

0.298

AC:

45203

AN:

151730

Hom.:

7172

Cov.:

AF XY:

0.305

AC XY:

22651

AN XY:

74152

show subpopulations

Gnomad4 AFR

AF:

0.341

Gnomad4 AMR

AF:

0.237

Gnomad4 ASJ

AF:

0.193

Gnomad4 EAS

AF:

0.179

Gnomad4 SAS

AF:

0.381

Gnomad4 FIN

AF:

0.465

Gnomad4 NFE

AF:

0.267

Gnomad4 OTH

AF:

0.264

Alfa

AF:

0.262

Hom.:

12052

Bravo

AF:

0.278

Asia WGS

AF:

0.311

AC:

1080

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 09, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.21

DANN

Benign

0.86

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over