rs121912722
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PP3_Moderate
The NM_000039.3(APOA1):āc.566C>Gā(p.Pro189Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000436 in 1,604,644 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Consequence
NM_000039.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
APOA1 | NM_000039.3 | c.566C>G | p.Pro189Arg | missense_variant | Exon 4 of 4 | ENST00000236850.5 | NP_000030.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152214Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000418 AC: 1AN: 239404Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 131102
GnomAD4 exome AF: 0.00000413 AC: 6AN: 1452430Hom.: 0 Cov.: 32 AF XY: 0.00000277 AC XY: 2AN XY: 722440
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152214Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74358
ClinVar
Submissions by phenotype
Apolipoprotein A-I deficiency Pathogenic:1
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not provided Uncertain:1
This sequence change replaces proline, which is neutral and non-polar, with arginine, which is basic and polar, at codon 189 of the APOA1 protein (p.Pro189Arg). This variant is present in population databases (rs121912722, gnomAD 0.0009%). This missense change has been observed in individual(s) with apolipoprotein A1 deficiency and/or low HDL-C (PMID: 2512329, 28870971). This variant is also known as Pro165Arg. ClinVar contains an entry for this variant (Variation ID: 17916). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt APOA1 protein function with a positive predictive value of 80%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at