rs17885558

chr7-95359938-G-Achr7-95359938-G-Cchr7-95359938-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000940.3(PON3):c.*35C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.012 in 1,526,216 control chromosomes in the GnomAD database, including 321 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.027 (106 hom., cov: 32)
  • Exomes 𝑓: 0.010 (215 hom.)
• Consequence: PON3 NM_000940.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.738

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0644 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PON3	NM_000940.3	c.*35C>T		3_prime_UTR_variant	9/9	ENST00000265627.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PON3	ENST00000265627.10	c.*35C>T		3_prime_UTR_variant	9/9	1	NM_000940.3	P1

Frequencies

GnomAD3 genomes AF: 0.0269 AC: 4023 AN: 149418 Hom.: 103 Cov.: 32

Gnomad AFR AF: 0.0662

Gnomad AMI AF: 0.00440

Gnomad AMR AF: 0.0175

Gnomad ASJ AF: 0.00406

Gnomad EAS AF: 0.0266

Gnomad SAS AF: 0.0216

Gnomad FIN AF: 0.0254

Gnomad MID AF: 0.0132

Gnomad NFE AF: 0.00778

Gnomad OTH AF: 0.0204

GnomAD3 exomes AF: 0.0108 AC: 2469 AN: 227666 Hom.: 50 AF XY: 0.0102 AC XY: 1278 AN XY: 124764

Gnomad AFR exome AF: 0.0461

Gnomad AMR exome AF: 0.0116

Gnomad ASJ exome AF: 0.00353

Gnomad EAS exome AF: 0.0161

Gnomad SAS exome AF: 0.0162

Gnomad FIN exome AF: 0.0107

Gnomad NFE exome AF: 0.00479

Gnomad OTH exome AF: 0.00757

GnomAD4 exome AF: 0.0104 AC: 14326 AN: 1376730 Hom.: 215 Cov.: 28 AF XY: 0.0106 AC XY: 7290 AN XY: 688038

Gnomad4 AFR exome AF: 0.0657

Gnomad4 AMR exome AF: 0.0124

Gnomad4 ASJ exome AF: 0.00423

Gnomad4 EAS exome AF: 0.0357

Gnomad4 SAS exome AF: 0.0191

Gnomad4 FIN exome AF: 0.0208

Gnomad4 NFE exome AF: 0.00654

Gnomad4 OTH exome AF: 0.0151

GnomAD4 genome AF: 0.0270 AC: 4039 AN: 149486 Hom.: 106 Cov.: 32 AF XY: 0.0273 AC XY: 1993 AN XY: 72914

Gnomad4 AFR AF: 0.0665

Gnomad4 AMR AF: 0.0174

Gnomad4 ASJ AF: 0.00406

Gnomad4 EAS AF: 0.0269

Gnomad4 SAS AF: 0.0215

Gnomad4 FIN AF: 0.0254

Gnomad4 NFE AF: 0.00778

Gnomad4 OTH AF: 0.0198

Alfa AF: 0.00999 Hom.: 31

Bravo AF: 0.0287

Asia WGS AF: 0.0280 AC: 95 AN: 3448

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	0.83
Dann	Benign	0.62

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs17885558; hg19: chr7-94989250;