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rs1053275

chr7-95372243-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_000940.3(PON3):c.297G>A(p.Ala99=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.512 in 1,612,772 control chromosomes in the GnomAD database, including 218,407 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.54 ( 22797 hom., cov: 32)
Exomes 𝑓: 0.51 ( 195610 hom. )

Consequence

PON3
NM_000940.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0810
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.73).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 7-95372243-C-T is Benign according to our data. Variant chr7-95372243-C-T is described in ClinVar as [Benign]. Clinvar id is 1289181.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.081 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.762 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PON3NM_000940.3 linkuse as main transcriptc.297G>A p.Ala99= synonymous_variant 4/9 ENST00000265627.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PON3ENST00000265627.10 linkuse as main transcriptc.297G>A p.Ala99= synonymous_variant 4/91 NM_000940.3 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.541
AC:
82082
AN:
151792
Hom.:
22743
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.572
Gnomad AMI
AF:
0.618
Gnomad AMR
AF:
0.613
Gnomad ASJ
AF:
0.418
Gnomad EAS
AF:
0.782
Gnomad SAS
AF:
0.690
Gnomad FIN
AF:
0.627
Gnomad MID
AF:
0.440
Gnomad NFE
AF:
0.470
Gnomad OTH
AF:
0.516
GnomAD3 exomes
AF:
0.571
AC:
143582
AN:
251258
Hom.:
43001
AF XY:
0.569
AC XY:
77217
AN XY:
135810
show subpopulations
Gnomad AFR exome
AF:
0.580
Gnomad AMR exome
AF:
0.713
Gnomad ASJ exome
AF:
0.405
Gnomad EAS exome
AF:
0.786
Gnomad SAS exome
AF:
0.683
Gnomad FIN exome
AF:
0.607
Gnomad NFE exome
AF:
0.473
Gnomad OTH exome
AF:
0.525
GnomAD4 exome
AF:
0.509
AC:
744296
AN:
1460862
Hom.:
195610
Cov.:
49
AF XY:
0.513
AC XY:
372834
AN XY:
726788
show subpopulations
Gnomad4 AFR exome
AF:
0.585
Gnomad4 AMR exome
AF:
0.698
Gnomad4 ASJ exome
AF:
0.407
Gnomad4 EAS exome
AF:
0.821
Gnomad4 SAS exome
AF:
0.677
Gnomad4 FIN exome
AF:
0.602
Gnomad4 NFE exome
AF:
0.473
Gnomad4 OTH exome
AF:
0.519
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.541
AC:
82194
AN:
151910
Hom.:
22797
Cov.:
32
AF XY:
0.555
AC XY:
41207
AN XY:
74234
show subpopulations
Gnomad4 AFR
AF:
0.573
Gnomad4 AMR
AF:
0.613
Gnomad4 ASJ
AF:
0.418
Gnomad4 EAS
AF:
0.782
Gnomad4 SAS
AF:
0.690
Gnomad4 FIN
AF:
0.627
Gnomad4 NFE
AF:
0.470
Gnomad4 OTH
AF:
0.521
Alfa
AF:
0.486
Hom.:
43724
Bravo
AF:
0.541
Asia WGS
AF:
0.737
AC:
2561
AN:
3476
EpiCase
AF:
0.464
EpiControl
AF:
0.468

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 submitterclinical testingGeneDxJun 09, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.73
Cadd
Benign
4.5
Dann
Benign
0.67

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.

Other links and lift over

dbSNP: rs1053275; hg19: chr7-95001555; COSMIC: COSV55699327; API