7-95359943-CTTTTTT-CTTTT

Variant names:

• chr7-95359943-CTT-C
• rs76171675
• NM_000940.3:c.*28_*29delAA

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BS1

The NM_000940.3(PON3):​c.*28_*29delAA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0268 in 1,383,802 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00038 (0 hom., cov: 30)
  • Exomes 𝑓: 0.030 (0 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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BS1: Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.0297 (37029/1245582) while in subpopulation AMR AF= 0.0346 (1233/35658). AF 95% confidence interval is 0.033. There are 0 homozygotes in gnomad4_exome. There are 18251 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PON3	NM_000940.3	c.*28_*29delAA		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.*28_*29delAA		3_prime_UTR_variant	Exon 9 of 9	1	NM_000940.3	ENSP00000265627.5

Frequencies

GnomAD3 genomes AF: 0.000369 AC: 51 AN: 138194 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.000158

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000513

Gnomad ASJ AF: 0.000308

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00222

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000269

Gnomad OTH AF: 0.00107

GnomAD4 exome AF: 0.0297 AC: 37029 AN: 1245582 Hom.: 0 AF XY: 0.0293 AC XY: 18251 AN XY: 622712

Gnomad4 AFR exome AF: 0.0267

Gnomad4 AMR exome AF: 0.0346

Gnomad4 ASJ exome AF: 0.0359

Gnomad4 EAS exome AF: 0.0309

Gnomad4 SAS exome AF: 0.0290

Gnomad4 FIN exome AF: 0.0316

Gnomad4 NFE exome AF: 0.0294

Gnomad4 OTH exome AF: 0.0312

GnomAD4 genome AF: 0.000376 AC: 52 AN: 138220 Hom.: 0 Cov.: 30 AF XY: 0.000344 AC XY: 23 AN XY: 66772

Gnomad4 AFR AF: 0.000158

Gnomad4 AMR AF: 0.000513

Gnomad4 ASJ AF: 0.000308

Gnomad4 EAS AF: 0.000208

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00222

Gnomad4 NFE AF: 0.000269

Gnomad4 OTH AF: 0.00107

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;