Variant 7-95362320-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.0110

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 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_multiple_submitters_no_conflicts, 2 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	Protein	UniProt
PON3	NM_000940.3 linkuse as main transcript	c.906+42A>G		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.906+42A>G		intron_variant		1	NM_000940.3	ENSP00000265627	P1

Frequencies

GnomAD3 genomes

AF:

0.184

AC:

28039

AN:

152096

Hom.:

3574

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.212

AC XY:

153789

AN XY:

725778

show subpopulations

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.:

AF XY:

0.190

AC XY:

14165

AN XY:

74422

show subpopulations

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:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

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 20, 2021	- -

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

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