Variant 7-95394734-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_000940.3(PON3):c.75-20T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.496 in 1,608,082 control chromosomes in the GnomAD database, including 203,332 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.52 ( 20701 hom., cov: 31)

Exomes 𝑓: 0.49 ( 182631 hom. )

Consequence

PON3
NM_000940.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.19

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 7-95394734-A-G is Benign according to our data. Variant chr7-95394734-A-G is described in ClinVar as [Benign]. Clinvar id is 1252233.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.742 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PON3	NM_000940.3 linkuse as main transcript	c.75-20T>C		intron_variant		ENST00000265627.10	NP_000931.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PON3	ENST00000265627.10 linkuse as main transcript	c.75-20T>C		intron_variant		1	NM_000940.3	ENSP00000265627	P1

Frequencies

GnomAD3 genomes

AF:

0.516

AC:

78353

AN:

151894

Hom.:

20663

Cov.:

show subpopulations

Gnomad AFR

AF:

0.521

Gnomad AMI

AF:

0.618

Gnomad AMR

AF:

0.581

Gnomad ASJ

AF:

0.412

Gnomad EAS

AF:

0.762

Gnomad SAS

AF:

0.642

Gnomad FIN

AF:

0.620

Gnomad MID

AF:

0.434

Gnomad NFE

AF:

0.459

Gnomad OTH

AF:

0.492

GnomAD3 exomes

AF:

0.548

AC:

137755

AN:

251222

Hom.:

39453

AF XY:

0.546

AC XY:

74152

AN XY:

135760

show subpopulations

Gnomad AFR exome

AF:

0.525

Gnomad AMR exome

AF:

0.668

Gnomad ASJ exome

AF:

0.397

Gnomad EAS exome

AF:

0.763

Gnomad SAS exome

AF:

0.638

Gnomad FIN exome

AF:

0.602

Gnomad NFE exome

AF:

0.462

Gnomad OTH exome

AF:

0.511

GnomAD4 exome

AF:

0.494

AC:

718820

AN:

1456070

Hom.:

182631

Cov.:

AF XY:

0.497

AC XY:

359968

AN XY:

724758

show subpopulations

Gnomad4 AFR exome

AF:

0.532

Gnomad4 AMR exome

AF:

0.655

Gnomad4 ASJ exome

AF:

0.400

Gnomad4 EAS exome

AF:

0.798

Gnomad4 SAS exome

AF:

0.632

Gnomad4 FIN exome

AF:

0.596

Gnomad4 NFE exome

AF:

0.461

Gnomad4 OTH exome

AF:

0.502

GnomAD4 genome

AF:

0.516

AC:

78452

AN:

152012

Hom.:

20701

Cov.:

AF XY:

0.530

AC XY:

39396

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.522

Gnomad4 AMR

AF:

0.581

Gnomad4 ASJ

AF:

0.412

Gnomad4 EAS

AF:

0.761

Gnomad4 SAS

AF:

0.642

Gnomad4 FIN

AF:

0.620

Gnomad4 NFE

AF:

0.459

Gnomad4 OTH

AF:

0.497

Alfa

AF:

0.471

Hom.:

17545

Bravo

AF:

0.514

Asia WGS

AF:

0.703

AC:

2442

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 19, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

DANN

Benign

0.53

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.21

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.21

Position offset: 2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over