rs10953146

Variant names:

• chr7-95394053-A-C
• rs10953146
• NM_000940.3:c.145+591T>G

Your query was ambiguous. Multiple possible variants found:

• chr7-95394053-A-C
• chr7-95394053-A-T

Variant summary

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

The NM_000940.3(PON3):​c.145+591T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.54 in 151,820 control chromosomes in the GnomAD database, including 22,670 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 0.54 (22670 hom., cov: 31)
• Consequence: PON3 NM_000940.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.967
• Publications: 4 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=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.763 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PON3	NM_000940.3	c.145+591T>G		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.145+591T>G		intron_variant	Intron 2 of 8	1	NM_000940.3	ENSP00000265627.5

Frequencies

GnomAD3 genomes AF: 0.539 AC: 81837 AN: 151702 Hom.: 22617 Cov.: 31

Gnomad AFR AF: 0.567

Gnomad AMI AF: 0.618

Gnomad AMR AF: 0.612

Gnomad ASJ AF: 0.418

Gnomad EAS AF: 0.783

Gnomad SAS AF: 0.691

Gnomad FIN AF: 0.626

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.470

Gnomad OTH AF: 0.518

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

GnomAD4 genome AF: 0.540 AC: 81948 AN: 151820 Hom.: 22670 Cov.: 31 AF XY: 0.554 AC XY: 41089 AN XY: 74190

African (AFR) AF: 0.568 AC: 23510 AN: 41378

American (AMR) AF: 0.613 AC: 9350 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.418 AC: 1451 AN: 3470

East Asian (EAS) AF: 0.783 AC: 4014 AN: 5124

South Asian (SAS) AF: 0.690 AC: 3321 AN: 4810

European-Finnish (FIN) AF: 0.626 AC: 6598 AN: 10542

Middle Eastern (MID) AF: 0.425 AC: 125 AN: 294

European-Non Finnish (NFE) AF: 0.470 AC: 31916 AN: 67930

Other (OTH) AF: 0.522 AC: 1101 AN: 2108

Alfa AF: 0.503 Hom.: 2416

Bravo AF: 0.539

Asia WGS AF: 0.738 AC: 2563 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.2
DANN	Benign	0.40
PhyloP100		-0.97
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: rs10953146; hg19: chr7-95023365;