rs142523546

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_000446.7(PON1):​c.781-301_781-300delTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 28)

Consequence

PON1
NM_000446.7 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0610

Publications

0 publications found
Variant links:
Genes affected
PON1 (HGNC:9204): (paraoxonase 1) This gene encodes a member of the paraoxonase family of enzymes and exhibits lactonase and ester hydrolase activity. Following synthesis in the kidney and liver, the enzyme is secreted into the circulation, where it binds to high density lipoprotein (HDL) particles and hydrolyzes thiolactones and xenobiotics, including paraoxon, a metabolite of the insecticide parathion. Polymorphisms in this gene may be associated with coronary artery disease and diabetic retinopathy. The gene is found in a cluster of three related paraoxonase genes on chromosome 7. [provided by RefSeq, Aug 2017]
PON1 Gene-Disease associations (from GenCC):
  • amyotrophic lateral sclerosis
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 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
PON1NM_000446.7 linkc.781-301_781-300delTT intron_variant Intron 7 of 8 ENST00000222381.8 NP_000437.3 P27169

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PON1ENST00000222381.8 linkc.781-301_781-300delTT intron_variant Intron 7 of 8 1 NM_000446.7 ENSP00000222381.3 P27169
PON1ENST00000433729.1 linkn.*506-301_*506-300delTT intron_variant Intron 7 of 8 3 ENSP00000407359.1 F8WF42
PON1ENST00000462594.1 linkn.-231_-230delTT upstream_gene_variant 2

Frequencies

GnomAD3 genomes
Cov.:
28
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
Cov.:
28

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
PhyloP100
0.061

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

Other links and lift over

dbSNP: rs142523546; hg19: chr7-94931944; API