7-95367478-C-T

Position:

• chr7-95367478-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_000940.3(PON3):​c.378G>A​(p.Val126Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00717 in 1,612,930 control chromosomes in the GnomAD database, including 643 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 0.036 (328 hom., cov: 33)
  • Exomes 𝑓: 0.0042 (315 hom.)
• Consequence: PON3 NM_000940.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0980

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP7: Synonymous conserved (PhyloP=0.098 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.122 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PON3	NM_000940.3	c.378G>A	p.Val126Val	synonymous_variant	5/9	ENST00000265627.10	NP_000931.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PON3	ENST00000265627.10	c.378G>A	p.Val126Val	synonymous_variant	5/9	1	NM_000940.3	ENSP00000265627.5

Frequencies

GnomAD3 genomes AF: 0.0360 AC: 5472 AN: 152108 Hom.: 326 Cov.: 33

Gnomad AFR AF: 0.125

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0141

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000676

Gnomad OTH AF: 0.0234

GnomAD3 exomes AF: 0.00982 AC: 2465 AN: 251054 Hom.: 150 AF XY: 0.00716 AC XY: 972 AN XY: 135680

Gnomad AFR exome AF: 0.128

Gnomad AMR exome AF: 0.00764

Gnomad ASJ exome AF: 0.000298

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000261

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000599

Gnomad OTH exome AF: 0.00653

GnomAD4 exome AF: 0.00416 AC: 6078 AN: 1460704 Hom.: 315 Cov.: 31 AF XY: 0.00368 AC XY: 2673 AN XY: 726728

Gnomad4 AFR exome AF: 0.130

Gnomad4 AMR exome AF: 0.00888

Gnomad4 ASJ exome AF: 0.000191

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000301

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000678

Gnomad4 OTH exome AF: 0.00868

GnomAD4 genome AF: 0.0360 AC: 5485 AN: 152226 Hom.: 328 Cov.: 33 AF XY: 0.0351 AC XY: 2612 AN XY: 74430

Gnomad4 AFR AF: 0.124

Gnomad4 AMR AF: 0.0141

Gnomad4 ASJ AF: 0.000576

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000676

Gnomad4 OTH AF: 0.0232

Alfa AF: 0.00590 Hom.: 82

Bravo AF: 0.0410

Asia WGS AF: 0.00866 AC: 30 AN: 3478

EpiCase AF: 0.000600

EpiControl AF: 0.000771

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	3.3
DANN	Benign	0.58

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: rs17879114; hg19: chr7-94996790;