Genetic Variant PON3:c.*27_*29dupAAA (chr7-95359943-C-CTTT) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_000940.3(PON3):c.*27_*29dupAAA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000287 in 1,464,800 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00033 ( 0 hom., cov: 30)

Exomes 𝑓: 0.00028 ( 0 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 Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PON3	NM_000940.3 link	c.27_29dupAAA		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.27_29dupAAA		3_prime_UTR_variant	Exon 9 of 9	1	NM_000940.3	ENSP00000265627.5		Q15166

Frequencies

GnomAD3 genomes

AF:

0.000325

AC:

AN:

138340

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000237

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000732

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00602

Gnomad SAS

AF:

0.000232

Gnomad FIN

AF:

0.000245

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000317

Gnomad OTH

AF:

0.000535

GnomAD4 exome

AF:

0.000283

AC:

376

AN:

1326434

Hom.:

Cov.:

AF XY:

0.000312

AC XY:

207

AN XY:

662806

show subpopulations

Gnomad4 AFR exome

AF:

0.00152

Gnomad4 AMR exome

AF:

0.000502

Gnomad4 ASJ exome

AF:

0.000164

Gnomad4 EAS exome

AF:

0.00155

Gnomad4 SAS exome

AF:

0.000689

Gnomad4 FIN exome

AF:

0.000414

Gnomad4 NFE exome

AF:

0.000156

Gnomad4 OTH exome

AF:

0.000378

GnomAD4 genome

AF:

0.000325

AC:

AN:

138366

Hom.:

Cov.:

AF XY:

0.000389

AC XY:

AN XY:

66852

show subpopulations

Gnomad4 AFR

AF:

0.000237

Gnomad4 AMR

AF:

0.0000732

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00603

Gnomad4 SAS

AF:

0.000233

Gnomad4 FIN

AF:

0.000245

Gnomad4 NFE

AF:

0.0000317

Gnomad4 OTH

AF:

0.000534

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.

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