Genetic Variant NM_000940.3: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:

Genome browser will be placed here

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.

NM_000940.3:c.27_29dupAAA

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