7-95359943-C-CT

Position:

• chr7-95359943-C-CT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_000940.3(PON3):​c.*29_*30insA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0486 in 1,452,720 control chromosomes in the GnomAD database, including 179 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.043 (162 hom., cov: 30)
  • Exomes 𝑓: 0.049 (17 hom.)
• Consequence: PON3 NM_000940.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.382

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 7-95359943-C-CT is Benign according to our data. Variant chr7-95359943-C-CT is described in ClinVar as [Benign]. Clinvar id is 1180951.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.061 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PON3	NM_000940.3	c.*29_*30insA		3_prime_UTR_variant	9/9	ENST00000265627.10	NP_000931.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PON3	ENST00000265627.10	c.*29_*30insA		3_prime_UTR_variant	9/9	1	NM_000940.3	ENSP00000265627	P1

Frequencies

GnomAD3 genomes AF: 0.0429 AC: 5938 AN: 138332 Hom.: 159 Cov.: 30

Gnomad AFR AF: 0.0628

Gnomad AMI AF: 0.00117

Gnomad AMR AF: 0.0476

Gnomad ASJ AF: 0.0194

Gnomad EAS AF: 0.0280

Gnomad SAS AF: 0.0562

Gnomad FIN AF: 0.0181

Gnomad MID AF: 0.0172

Gnomad NFE AF: 0.0353

Gnomad OTH AF: 0.0412

GnomAD4 exome AF: 0.0491 AC: 64598 AN: 1314362 Hom.: 17 Cov.: 0 AF XY: 0.0486 AC XY: 31900 AN XY: 656778

Gnomad4 AFR exome AF: 0.0694

Gnomad4 AMR exome AF: 0.0444

Gnomad4 ASJ exome AF: 0.0332

Gnomad4 EAS exome AF: 0.0424

Gnomad4 SAS exome AF: 0.0555

Gnomad4 FIN exome AF: 0.0271

Gnomad4 NFE exome AF: 0.0500

Gnomad4 OTH exome AF: 0.0487

GnomAD4 genome AF: 0.0431 AC: 5960 AN: 138358 Hom.: 162 Cov.: 30 AF XY: 0.0420 AC XY: 2808 AN XY: 66852

Gnomad4 AFR AF: 0.0631

Gnomad4 AMR AF: 0.0479

Gnomad4 ASJ AF: 0.0194

Gnomad4 EAS AF: 0.0281

Gnomad4 SAS AF: 0.0564

Gnomad4 FIN AF: 0.0181

Gnomad4 NFE AF: 0.0353

Gnomad4 OTH AF: 0.0422

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 20, 2021

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs76171675; hg19: chr7-94989255;