Variant 7-95360067-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_000940.3(PON3):c.971G>A(p.Gly324Asp) variant causes a missense change. The variant allele was found at a frequency of 0.00238 in 1,613,326 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0023 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0024 ( 6 hom. )

Consequence

PON3
NM_000940.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 6.96

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.02052787).

BP6

Variant 7-95360067-C-T is Benign according to our data. Variant chr7-95360067-C-T is described in ClinVar as [Benign]. Clinvar id is 708721.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PON3	NM_000940.3 linkuse as main transcript	c.971G>A	p.Gly324Asp	missense_variant	9/9	ENST00000265627.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PON3	ENST00000265627.10 linkuse as main transcript	c.971G>A	p.Gly324Asp	missense_variant	9/9	1	NM_000940.3	P1

Frequencies

GnomAD3 genomes

AF:

0.00230

AC:

349

AN:

151866

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000435

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000460

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0109

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00290

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.00268

AC:

673

AN:

251354

Hom.:

AF XY:

0.00257

AC XY:

349

AN XY:

135838

show subpopulations

Gnomad AFR exome

AF:

0.000308

Gnomad AMR exome

AF:

0.00116

Gnomad ASJ exome

AF:

0.00308

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.0105

Gnomad NFE exome

AF:

0.00302

Gnomad OTH exome

AF:

0.00359

GnomAD4 exome

AF:

0.00238

AC:

3483

AN:

1461344

Hom.:

Cov.:

AF XY:

0.00236

AC XY:

1717

AN XY:

727046

show subpopulations

Gnomad4 AFR exome

AF:

0.000448

Gnomad4 AMR exome

AF:

0.00127

Gnomad4 ASJ exome

AF:

0.00356

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000151

Gnomad4 FIN exome

AF:

0.0119

Gnomad4 NFE exome

AF:

0.00225

Gnomad4 OTH exome

AF:

0.00245

GnomAD4 genome

AF:

0.00230

AC:

349

AN:

151982

Hom.:

Cov.:

AF XY:

0.00261

AC XY:

194

AN XY:

74268

show subpopulations

Gnomad4 AFR

AF:

0.000434

Gnomad4 AMR

AF:

0.000459

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.0109

Gnomad4 NFE

AF:

0.00290

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00261

Hom.:

Bravo

AF:

0.00159

TwinsUK

AF:

0.00270

AC:

ALSPAC

AF:

0.00156

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00337

AC:

ExAC

AF:

0.00279

AC:

339

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00316

EpiControl

AF:

0.00320

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.84

BayesDel_addAF

Benign

-0.060

BayesDel_noAF

Pathogenic

0.14

Cadd

Pathogenic

Dann

Uncertain

1.0

DEOGEN2

Benign

0.36

Eigen

Pathogenic

0.88

Eigen_PC

Pathogenic

0.80

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Pathogenic

0.99

MetaRNN

Benign

0.021

MetaSVM

Uncertain

-0.23

MutationAssessor

Pathogenic

3.4

MutationTaster

Benign

1.0

D;D;D

PROVEAN

Pathogenic

-6.5

REVEL

Uncertain

0.50

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.95

MVP

0.82

MPC

0.39

ClinPred

0.066

GERP RS

4.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.93

gMVP

0.93

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