NM_000940.3:c.907-230G>A

Variant names:

• chr7-95360361-C-T
• rs2074352
• NM_000940.3:c.907-230G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000940.3(PON3):​c.907-230G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 152,118 control chromosomes in the GnomAD database, including 3,572 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.18 (3572 hom., cov: 32)
• Consequence: PON3 NM_000940.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.680
• Publications: 3 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 7-95360361-C-T is Benign according to our data. Variant chr7-95360361-C-T is described in ClinVar as Benign. ClinVar VariationId is 1249064.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.573 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000940.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PON3	NM_000940.3	MANE Select	c.907-230G>A		intron	N/A	NP_000931.1	Q15166

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PON3	ENST00000265627.10	TSL:1 MANE Select	c.907-230G>A		intron	N/A	ENSP00000265627.5	Q15166
	PON3	ENST00000902762.1		c.1090-230G>A		intron	N/A	ENSP00000572821.1
	PON3	ENST00000902763.1		c.1060-230G>A		intron	N/A	ENSP00000572822.1

Frequencies

GnomAD3 genomes AF: 0.184 AC: 28015 AN: 152000 Hom.: 3570 Cov.: 32

Gnomad AFR AF: 0.0654

Gnomad AMI AF: 0.140

Gnomad AMR AF: 0.329

Gnomad ASJ AF: 0.216

Gnomad EAS AF: 0.591

Gnomad SAS AF: 0.253

Gnomad FIN AF: 0.155

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.192

Gnomad OTH AF: 0.203

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

GnomAD4 genome AF: 0.184 AC: 28021 AN: 152118 Hom.: 3572 Cov.: 32 AF XY: 0.190 AC XY: 14156 AN XY: 74360

African (AFR) AF: 0.0652 AC: 2709 AN: 41522

American (AMR) AF: 0.329 AC: 5029 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.216 AC: 751 AN: 3472

East Asian (EAS) AF: 0.591 AC: 3051 AN: 5166

South Asian (SAS) AF: 0.254 AC: 1222 AN: 4818

European-Finnish (FIN) AF: 0.155 AC: 1637 AN: 10578

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.192 AC: 13019 AN: 67978

Other (OTH) AF: 0.204 AC: 430 AN: 2110

Alfa AF: 0.202 Hom.: 4370

Bravo AF: 0.197

Asia WGS AF: 0.380 AC: 1320 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.8
DANN	Benign	0.47
PhyloP100		-0.68
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs2074352; hg19: chr7-94989673;