rs756985434
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PP2PP3BS2_Supporting
The NM_002734.5(PRKAR1A):c.94A>G(p.Lys32Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000496 in 1,613,416 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 (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K32R) has been classified as Uncertain significance.
Frequency
Consequence
NM_002734.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PRKAR1A | NM_002734.5 | c.94A>G | p.Lys32Glu | missense_variant | 2/11 | ENST00000589228.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRKAR1A | ENST00000589228.6 | c.94A>G | p.Lys32Glu | missense_variant | 2/11 | 1 | NM_002734.5 | P1 | |
ENST00000590353.1 | n.273A>G | non_coding_transcript_exon_variant | 2/6 | 4 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152234Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000795 AC: 2AN: 251424Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135890
GnomAD4 exome AF: 0.00000479 AC: 7AN: 1461182Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3AN XY: 726908
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152234Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74372
ClinVar
Submissions by phenotype
Acrodysostosis 1 with or without hormone resistance Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Nov 30, 2023 | - - |
Carney complex, type 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 15, 2024 | This sequence change replaces lysine, which is basic and polar, with glutamic acid, which is acidic and polar, at codon 32 of the PRKAR1A protein (p.Lys32Glu). This variant is present in population databases (rs756985434, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with PRKAR1A-related conditions. ClinVar contains an entry for this variant (Variation ID: 469080). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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. - |
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 24, 2023 | The p.K32E variant (also known as c.94A>G), located in coding exon 1 of the PRKAR1A gene, results from an A to G substitution at nucleotide position 94. The lysine at codon 32 is replaced by glutamic acid, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at