17-68512458-G-A
Variant names:
Variant summary
Our verdict is Uncertain significance. The variant received 3 ACMG points: 4P and 1B. PM2PP5_ModerateBP4
The NM_002734.5(PRKAR1A):c.-97G>A variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★).
Frequency
Genomes: not found (cov: 32)
Consequence
PRKAR1A
NM_002734.5 5_prime_UTR_premature_start_codon_gain
NM_002734.5 5_prime_UTR_premature_start_codon_gain
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.617
Publications
0 publications found
Genes affected
PRKAR1A (HGNC:9388): (protein kinase cAMP-dependent type I regulatory subunit alpha) cAMP is a signaling molecule important for a variety of cellular functions. cAMP exerts its effects by activating the cAMP-dependent protein kinase, which transduces the signal through phosphorylation of different target proteins. The inactive kinase holoenzyme is a tetramer composed of two regulatory and two catalytic subunits. cAMP causes the dissociation of the inactive holoenzyme into a dimer of regulatory subunits bound to four cAMP and two free monomeric catalytic subunits. Four different regulatory subunits and three catalytic subunits have been identified in humans. This gene encodes one of the regulatory subunits. This protein was found to be a tissue-specific extinguisher that down-regulates the expression of seven liver genes in hepatoma x fibroblast hybrids. Mutations in this gene cause Carney complex (CNC). This gene can fuse to the RET protooncogene by gene rearrangement and form the thyroid tumor-specific chimeric oncogene known as PTC2. A nonconventional nuclear localization sequence (NLS) has been found for this protein which suggests a role in DNA replication via the protein serving as a nuclear transport protein for the second subunit of the Replication Factor C (RFC40). Several alternatively spliced transcript variants encoding two different isoforms have been observed. [provided by RefSeq, Jan 2013]
PRKAR1A Gene-Disease associations (from GenCC):
- Acrodysostosis 1 with or without hormone resistanceInheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
- acrodysostosis with multiple hormone resistanceInheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Illumina, Orphanet
- Carney complex, type 1Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae)
- pigmented nodular adrenocortical disease, primary, 1Inheritance: AD Classification: STRONG, MODERATE Submitted by: Genomics England PanelApp, Ambry Genetics
- acrodysostosisInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- Carney complexInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- familial atrial myxomaInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- primary pigmented nodular adrenocortical diseaseInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 17-68512458-G-A is Pathogenic according to our data. Variant chr17-68512458-G-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 3780922.Status of the report is criteria_provided_single_submitter, 1 stars.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.56). . Strength limited to SUPPORTING due to the PP5.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PRKAR1A | NM_002734.5 | c.-97G>A | 5_prime_UTR_premature_start_codon_gain_variant | Exon 1 of 11 | ENST00000589228.6 | NP_002725.1 | ||
PRKAR1A | NM_002734.5 | c.-97G>A | 5_prime_UTR_variant | Exon 1 of 11 | ENST00000589228.6 | NP_002725.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PRKAR1A | ENST00000589228.6 | c.-97G>A | 5_prime_UTR_premature_start_codon_gain_variant | Exon 1 of 11 | 1 | NM_002734.5 | ENSP00000464977.2 | |||
PRKAR1A | ENST00000589228.6 | c.-97G>A | 5_prime_UTR_variant | Exon 1 of 11 | 1 | NM_002734.5 | ENSP00000464977.2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Cov.: 0
GnomAD4 exome
Cov.:
0
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Carney complex, type 1 Pathogenic:1
-
Department of Pathology and Laboratory Medicine, Sinai Health System
Significance:Likely pathogenic
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.