dbSNP rs17885558: PON3:c.*35C>T (chr7-95359938-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000940.3(PON3):c.*35C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.012 in 1,526,216 control chromosomes in the GnomAD database, including 321 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.027 ( 106 hom., cov: 32)

Exomes 𝑓: 0.010 ( 215 hom. )

Consequence

PON3
NM_000940.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.738

Publications

6 publications found

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 Gene-Disease associations (from GenCC):

amyotrophic lateral sclerosis
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

PON3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0644 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PON3	NM_000940.3 link	c.*35C>T		3_prime_UTR_variant	Exon 9 of 9	ENST00000265627.10	NP_000931.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PON3	ENST00000265627.10 link	c.*35C>T		3_prime_UTR_variant	Exon 9 of 9	1	NM_000940.3	ENSP00000265627.5

Frequencies

GnomAD3 genomes

AF:

0.0269

AC:

4023

AN:

149418

Hom.:

103

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0662

Gnomad AMI

AF:

0.00440

Gnomad AMR

AF:

0.0175

Gnomad ASJ

AF:

0.00406

Gnomad EAS

AF:

0.0266

Gnomad SAS

AF:

0.0216

Gnomad FIN

AF:

0.0254

Gnomad MID

AF:

0.0132

Gnomad NFE

AF:

0.00778

Gnomad OTH

AF:

0.0204

GnomAD2 exomes

AF:

0.0108

AC:

2469

AN:

227666

AF XY:

0.0102

show subpopulations

Gnomad AFR exome

AF:

0.0461

Gnomad AMR exome

AF:

0.0116

Gnomad ASJ exome

AF:

0.00353

Gnomad EAS exome

AF:

0.0161

Gnomad FIN exome

AF:

0.0107

Gnomad NFE exome

AF:

0.00479

Gnomad OTH exome

AF:

0.00757

GnomAD4 exome

AF:

0.0104

AC:

14326

AN:

1376730

Hom.:

215

Cov.:

AF XY:

0.0106

AC XY:

7290

AN XY:

688038

show subpopulations

African (AFR)

AF:

0.0657

AC:

2002

AN:

30466

American (AMR)

AF:

0.0124

AC:

527

AN:

42420

Ashkenazi Jewish (ASJ)

AF:

0.00423

AC:

107

AN:

25310

East Asian (EAS)

AF:

0.0357

AC:

1387

AN:

38884

South Asian (SAS)

AF:

0.0191

AC:

1553

AN:

81306

European-Finnish (FIN)

AF:

0.0208

AC:

988

AN:

47404

Middle Eastern (MID)

AF:

0.00782

AC:

AN:

5502

European-Non Finnish (NFE)

AF:

0.00654

AC:

6849

AN:

1047950

Other (OTH)

AF:

0.0151

AC:

870

AN:

57488

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.431

Heterozygous variant carriers

616

1232

1849

2465

3081

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

310

620

930

1240

1550

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0270

AC:

4039

AN:

149486

Hom.:

106

Cov.:

AF XY:

0.0273

AC XY:

1993

AN XY:

72914

show subpopulations

African (AFR)

AF:

0.0665

AC:

2701

AN:

40610

American (AMR)

AF:

0.0174

AC:

262

AN:

15020

Ashkenazi Jewish (ASJ)

AF:

0.00406

AC:

AN:

3450

East Asian (EAS)

AF:

0.0269

AC:

137

AN:

5092

South Asian (SAS)

AF:

0.0215

AC:

101

AN:

4704

European-Finnish (FIN)

AF:

0.0254

AC:

250

AN:

9836

Middle Eastern (MID)

AF:

0.0144

AC:

AN:

278

European-Non Finnish (NFE)

AF:

0.00778

AC:

525

AN:

67512

Other (OTH)

AF:

0.0198

AC:

AN:

2074

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

174

347

521

694

868

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

144

192

240

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0138

Hom.:

148

Bravo

AF:

0.0287

Asia WGS

AF:

0.0280

AC:

AN:

3448

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.83

(source)

DANN

Benign

0.62

PhyloP100

-0.74

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over