7-95362320-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000940.3(PON3):c.906+42A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.21 in 1,610,854 control chromosomes in the GnomAD database, including 41,992 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.18 (3576 hom., cov: 33)
  • Exomes 𝑓: 0.21 (38416 hom.)
• Consequence: PON3 NM_000940.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0110

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 7-95362320-T-C is Benign according to our data. Variant chr7-95362320-T-C is described in ClinVar as [Benign]. Clinvar id is 1242524.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.574 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PON3	NM_000940.3	c.906+42A>G		intron_variant		ENST00000265627.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PON3	ENST00000265627.10	c.906+42A>G		intron_variant		1	NM_000940.3	P1

Frequencies

GnomAD3 genomes AF: 0.184 AC: 28039 AN: 152096 Hom.: 3574 Cov.: 33

Gnomad AFR AF: 0.0654

Gnomad AMI AF: 0.141

Gnomad AMR AF: 0.328

Gnomad ASJ AF: 0.216

Gnomad EAS AF: 0.591

Gnomad SAS AF: 0.254

Gnomad FIN AF: 0.155

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.192

Gnomad OTH AF: 0.203

GnomAD3 exomes AF: 0.253 AC: 63059 AN: 249484 Hom.: 10516 AF XY: 0.246 AC XY: 33194 AN XY: 134820

Gnomad AFR exome AF: 0.0599

Gnomad AMR exome AF: 0.441

Gnomad ASJ exome AF: 0.209

Gnomad EAS exome AF: 0.605

Gnomad SAS exome AF: 0.240

Gnomad FIN exome AF: 0.154

Gnomad NFE exome AF: 0.193

Gnomad OTH exome AF: 0.234

GnomAD4 exome AF: 0.212 AC: 309703 AN: 1458640 Hom.: 38416 Cov.: 33 AF XY: 0.212 AC XY: 153789 AN XY: 725778

Gnomad4 AFR exome AF: 0.0536

Gnomad4 AMR exome AF: 0.424

Gnomad4 ASJ exome AF: 0.210

Gnomad4 EAS exome AF: 0.614

Gnomad4 SAS exome AF: 0.235

Gnomad4 FIN exome AF: 0.155

Gnomad4 NFE exome AF: 0.195

Gnomad4 OTH exome AF: 0.217

GnomAD4 genome AF: 0.184 AC: 28045 AN: 152214 Hom.: 3576 Cov.: 33 AF XY: 0.190 AC XY: 14165 AN XY: 74422

Gnomad4 AFR AF: 0.0652

Gnomad4 AMR AF: 0.329

Gnomad4 ASJ AF: 0.216

Gnomad4 EAS AF: 0.591

Gnomad4 SAS AF: 0.254

Gnomad4 FIN AF: 0.155

Gnomad4 NFE AF: 0.192

Gnomad4 OTH AF: 0.204

Alfa AF: 0.206 Hom.: 3317

Bravo AF: 0.197

Asia WGS AF: 0.380 AC: 1320 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 20, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	3.0
Dann	Benign	0.63

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: rs17884000; hg19: chr7-94991632; COSMIC: COSV55698528; COSMIC: COSV55698528;