rs10487132

Variant names:

• chr7-95390993-A-G
• rs10487132
• NM_000940.3:c.146-784T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000940.3(PON3):​c.146-784T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.294 in 152,046 control chromosomes in the GnomAD database, including 8,067 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.29 (8067 hom., cov: 32)
• Consequence: PON3 NM_000940.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.481
• Publications: 15 publications found

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 Gene-Disease associations (from GenCC):

• amyotrophic lateral sclerosis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.412 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PON3	NM_000940.3	c.146-784T>C		intron_variant	Intron 2 of 8	ENST00000265627.10	NP_000931.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PON3	ENST00000265627.10	c.146-784T>C		intron_variant	Intron 2 of 8	1	NM_000940.3	ENSP00000265627.5

Frequencies

GnomAD3 genomes AF: 0.295 AC: 44746 AN: 151928 Hom.: 8070 Cov.: 32

Gnomad AFR AF: 0.125

Gnomad AMI AF: 0.314

Gnomad AMR AF: 0.280

Gnomad ASJ AF: 0.467

Gnomad EAS AF: 0.00559

Gnomad SAS AF: 0.232

Gnomad FIN AF: 0.292

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.416

Gnomad OTH AF: 0.347

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

GnomAD4 genome AF: 0.294 AC: 44736 AN: 152046 Hom.: 8067 Cov.: 32 AF XY: 0.286 AC XY: 21240 AN XY: 74326

African (AFR) AF: 0.125 AC: 5189 AN: 41504

American (AMR) AF: 0.279 AC: 4260 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.467 AC: 1622 AN: 3472

East Asian (EAS) AF: 0.00579 AC: 30 AN: 5178

South Asian (SAS) AF: 0.232 AC: 1117 AN: 4808

European-Finnish (FIN) AF: 0.292 AC: 3087 AN: 10566

Middle Eastern (MID) AF: 0.480 AC: 141 AN: 294

European-Non Finnish (NFE) AF: 0.416 AC: 28279 AN: 67946

Other (OTH) AF: 0.344 AC: 725 AN: 2110

Alfa AF: 0.386 Hom.: 17344

Bravo AF: 0.285

Asia WGS AF: 0.105 AC: 370 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	9.9
DANN	Benign	0.47
PhyloP100		0.48
Mutation Taster		=100/0	polymorphism (auto)

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: rs10487132; hg19: chr7-95020305;