Genetic Variant PON3:c.*28_*29dupAA (chr7-95359943-C-CTT) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_000940.3(PON3):c.*28_*29dupAA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00851 in 1,460,498 control chromosomes in the GnomAD database, including 112 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.029 ( 105 hom., cov: 30)

Exomes 𝑓: 0.0064 ( 7 hom. )

Consequence

PON3
NM_000940.3 3_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.382

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 -8 ACMG points.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0679 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PON3	NM_000940.3 link	c.28_29dupAA		3_prime_UTR_variant	Exon 9 of 9	ENST00000265627.10	NP_000931.1	Q15166

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PON3	ENST00000265627 link	c.28_29dupAA		3_prime_UTR_variant	Exon 9 of 9	1	NM_000940.3	ENSP00000265627.5		Q15166

Frequencies

GnomAD3 genomes

AF:

0.0287

AC:

3974

AN:

138290

Hom.:

104

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0699

Gnomad AMI

AF:

0.00466

Gnomad AMR

AF:

0.0207

Gnomad ASJ

AF:

0.00586

Gnomad EAS

AF:

0.0216

Gnomad SAS

AF:

0.0230

Gnomad FIN

AF:

0.0294

Gnomad MID

AF:

0.0138

Gnomad NFE

AF:

0.00834

Gnomad OTH

AF:

0.0225

GnomAD4 exome

AF:

0.00639

AC:

8443

AN:

1322182

Hom.:

Cov.:

AF XY:

0.00642

AC XY:

4239

AN XY:

660648

show subpopulations

Gnomad4 AFR exome

AF:

0.0377

Gnomad4 AMR exome

AF:

0.00762

Gnomad4 ASJ exome

AF:

0.00424

Gnomad4 EAS exome

AF:

0.0166

Gnomad4 SAS exome

AF:

0.0110

Gnomad4 FIN exome

AF:

0.0109

Gnomad4 NFE exome

AF:

0.00446

Gnomad4 OTH exome

AF:

0.00885

GnomAD4 genome

AF:

0.0288

AC:

3984

AN:

138316

Hom.:

105

Cov.:

AF XY:

0.0293

AC XY:

1956

AN XY:

66826

show subpopulations

Gnomad4 AFR

AF:

0.0701

Gnomad4 AMR

AF:

0.0206

Gnomad4 ASJ

AF:

0.00586

Gnomad4 EAS

AF:

0.0218

Gnomad4 SAS

AF:

0.0228

Gnomad4 FIN

AF:

0.0294

Gnomad4 NFE

AF:

0.00834

Gnomad4 OTH

AF:

0.0219

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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.

7-95359943-CTTTTTT-CTTTTTTTT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over