NM_000940.3:c.*26_*29dupAAAA

Variant names:

• chr7-95359943-C-CTTTT
• rs76171675
• NM_000940.3:c.*26_*29dupAAAA

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_000940.3(PON3):​c.*26_*29dupAAAA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000234 in 1,327,010 control chromosomes in the GnomAD database, including 1 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.000023 (1 hom.)
• Consequence: PON3 NM_000940.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• 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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PON3	NM_000940.3	c.*26_*29dupAAAA		3_prime_UTR_variant	Exon 9 of 9	ENST00000265627.10	NP_000931.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PON3	ENST00000265627	c.*26_*29dupAAAA		3_prime_UTR_variant	Exon 9 of 9	1	NM_000940.3	ENSP00000265627.5

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 0.0000234 AC: 31 AN: 1327010 Hom.: 1 Cov.: 0 AF XY: 0.0000287 AC XY: 19 AN XY: 663078

Gnomad4 AFR exome AF: 0.000104

Gnomad4 AMR exome AF: 0.0000529

Gnomad4 ASJ exome AF: 0.0000410

Gnomad4 EAS exome AF: 0.0000800

Gnomad4 SAS exome AF: 0.000104

Gnomad4 FIN exome AF: 0.0000230

Gnomad4 NFE exome AF: 0.0000108

Gnomad4 OTH exome AF: 0.0000360

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

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;