7-95362932-T-C

Position:

• chr7-95362932-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000940.3(PON3):​c.696-91A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.481 in 839,564 control chromosomes in the GnomAD database, including 102,852 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.44 (15799 hom., cov: 32)
  • Exomes 𝑓: 0.49 (87053 hom.)
• Consequence: PON3 NM_000940.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.263

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 7-95362932-T-C is Benign according to our data. Variant chr7-95362932-T-C is described in ClinVar as [Benign]. Clinvar id is 1246197.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.719 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PON3	NM_000940.3	c.696-91A>G		intron_variant		ENST00000265627.10	NP_000931.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PON3	ENST00000265627.10	c.696-91A>G		intron_variant		1	NM_000940.3	ENSP00000265627.5

Frequencies

GnomAD3 genomes AF: 0.441 AC: 66919 AN: 151830 Hom.: 15792 Cov.: 32

Gnomad AFR AF: 0.292

Gnomad AMI AF: 0.613

Gnomad AMR AF: 0.541

Gnomad ASJ AF: 0.404

Gnomad EAS AF: 0.739

Gnomad SAS AF: 0.618

Gnomad FIN AF: 0.591

Gnomad MID AF: 0.399

Gnomad NFE AF: 0.450

Gnomad OTH AF: 0.433

GnomAD4 exome AF: 0.490 AC: 337194 AN: 687616 Hom.: 87053 AF XY: 0.495 AC XY: 181714 AN XY: 367412

Gnomad4 AFR exome AF: 0.293

Gnomad4 AMR exome AF: 0.621

Gnomad4 ASJ exome AF: 0.390

Gnomad4 EAS exome AF: 0.770

Gnomad4 SAS exome AF: 0.606

Gnomad4 FIN exome AF: 0.566

Gnomad4 NFE exome AF: 0.446

Gnomad4 OTH exome AF: 0.467

GnomAD4 genome AF: 0.441 AC: 66947 AN: 151948 Hom.: 15799 Cov.: 32 AF XY: 0.455 AC XY: 33813 AN XY: 74262

Gnomad4 AFR AF: 0.292

Gnomad4 AMR AF: 0.541

Gnomad4 ASJ AF: 0.404

Gnomad4 EAS AF: 0.738

Gnomad4 SAS AF: 0.619

Gnomad4 FIN AF: 0.591

Gnomad4 NFE AF: 0.450

Gnomad4 OTH AF: 0.439

Alfa AF: 0.454 Hom.: 33126

Bravo AF: 0.430

Asia WGS AF: 0.649 AC: 2256 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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 19, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.0
DANN	Benign	0.53

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: rs10953143; hg19: chr7-94992244; COSMIC: COSV55698580; COSMIC: COSV55698580;