rs201544566
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_000940.3(PON3):c.496G>A(p.Val166Met) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000418 in 1,613,394 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_000940.3 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PON3 | NM_000940.3 | c.496G>A | p.Val166Met | missense_variant, splice_region_variant | 6/9 | ENST00000265627.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PON3 | ENST00000265627.10 | c.496G>A | p.Val166Met | missense_variant, splice_region_variant | 6/9 | 1 | NM_000940.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000342 AC: 52AN: 152132Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000696 AC: 174AN: 250066Hom.: 1 AF XY: 0.000725 AC XY: 98AN XY: 135212
GnomAD4 exome AF: 0.000426 AC: 622AN: 1461144Hom.: 5 Cov.: 30 AF XY: 0.000453 AC XY: 329AN XY: 726906
GnomAD4 genome ? AF: 0.000342 AC: 52AN: 152250Hom.: 0 Cov.: 32 AF XY: 0.000363 AC XY: 27AN XY: 74448
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 31, 2018 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Mar 17, 2017 | The V166M variant in the PON3 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The V166M variant is observed in 26/11478 (0.2%) alleles from individuals of Latino background, and in 41/66332 (0.06%) alleles from individuals of European background, in the ExAC dataset (Lek et al., 2016). The V166M variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position where amino acids with similar properties to Valine are tolerated across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret V166M as a variant of uncertain significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at