7-95305886-CA-CAA

Variant names:

• chr7-95305886-C-CA
• rs3917549
• NM_000446.7:c.780+398dupT

Variant summary

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

The NM_000446.7(PON1):​c.780+398dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 19)
• Consequence: PON1 NM_000446.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.405
• Publications: 0 publications found

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PON1	NM_000446.7	c.780+398dupT		intron_variant	Intron 7 of 8	ENST00000222381.8	NP_000437.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PON1	ENST00000222381.8	c.780+398_780+399insT		intron_variant	Intron 7 of 8	1	NM_000446.7	ENSP00000222381.3
PON1	ENST00000433729.1	n.*505+398_*505+399insT		intron_variant	Intron 7 of 8	3		ENSP00000407359.1

Frequencies

GnomAD3 genomes Cov.: 19

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 19

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.41

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

Other links and lift over

dbSNP: rs3917549; hg19: chr7-94935198;