rs13226149

Positions:

• chr7-95396288-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.77

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]

ACMG classification

Verdict is Benign. Variant got -15 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_single_submitter, 1 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	UniProt
PON3	NM_000940.3	c.63C>T	p.Phe21=	synonymous_variant	1/9	ENST00000265627.10

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.298 AC: 45165 AN: 151612 Hom.: 7158 Cov.: 30

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

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.: 35 AF XY: 0.280 AC XY: 203898 AN XY: 727114

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.: 30 AF XY: 0.305 AC XY: 22651 AN XY: 74152

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:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

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

Other links and lift over

dbSNP: rs13226149; hg19: chr7-95025600; COSMIC: COSV55698518; COSMIC: COSV55698518;