17-68515520-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate
The NM_002734.5(PRKAR1A):c.121G>A(p.Ala41Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000031 in 1,613,030 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign 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. A41D) 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.121G>A | p.Ala41Thr | missense_variant | 2/11 | ENST00000589228.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRKAR1A | ENST00000589228.6 | c.121G>A | p.Ala41Thr | missense_variant | 2/11 | 1 | NM_002734.5 | P1 | |
ENST00000590353.1 | n.300G>A | non_coding_transcript_exon_variant | 2/6 | 4 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152198Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251382Hom.: 1 AF XY: 0.00 AC XY: 0AN XY: 135860
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1460832Hom.: 1 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 726738
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152198Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74368
ClinVar
Submissions by phenotype
Carney complex, type 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 20, 2022 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 536893). This variant has not been reported in the literature in individuals affected with PRKAR1A-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.01%). This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 41 of the PRKAR1A protein (p.Ala41Thr). - |
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 05, 2019 | The p.A41T variant (also known as c.121G>A), located in coding exon 1 of the PRKAR1A gene, results from a G to A substitution at nucleotide position 121. The alanine at codon 41 is replaced by threonine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated 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