7-95359943-CTTTTTT-CTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT

Variant names:

• chr7-95359943-C-CTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT
• rs76171675
• NM_000940.3:c.*29_*30insAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_000940.3(PON3):​c.*29_*30insAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000754 in 1,327,074 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 7.5e-7 (0 hom.)
• Consequence: PON3 NM_000940.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.382
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

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.*29_*30insAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA		3_prime_UTR	Exon 9 of 9	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.*29_*30insAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA		3_prime_UTR	Exon 9 of 9	ENSP00000265627.5	Q15166
	PON3	ENST00000427422.5	TSL:3	c.*145_*146insAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA		splice_region	Exon 7 of 7	ENSP00000413276.1	C9JZ99
	PON3	ENST00000902762.1		c.*29_*30insAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA		3_prime_UTR	Exon 10 of 10	ENSP00000572821.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 7.54e-7 AC: 1 AN: 1327074 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 663124

African (AFR) AF: 0.00 AC: 0 AN: 28922

American (AMR) AF: 0.00 AC: 0 AN: 37840

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24392

East Asian (EAS) AF: 0.00 AC: 0 AN: 37516

South Asian (SAS) AF: 0.00 AC: 0 AN: 77034

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43478

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5154

European-Non Finnish (NFE) AF: 9.83e-7 AC: 1 AN: 1017176

Other (OTH) AF: 0.00 AC: 0 AN: 55562

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.38

Splicing

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

Other links and lift over

dbSNP: rs76171675; hg19: chr7-94989255;