chr19-14102831-G-C
Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2
The NM_002730.4(PRKACA):c.321C>G(p.Leu107=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000967 in 1,614,040 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.000098 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000096 ( 0 hom. )
Consequence
PRKACA
NM_002730.4 synonymous
NM_002730.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.818
Genes affected
PRKACA (HGNC:9380): (protein kinase cAMP-activated catalytic subunit alpha) This gene encodes one of the catalytic subunits of protein kinase A, which exists as a tetrameric holoenzyme with two regulatory subunits and two catalytic subunits, in its inactive form. 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. cAMP-dependent phosphorylation of proteins by protein kinase A is important to many cellular processes, including differentiation, proliferation, and apoptosis. Constitutive activation of this gene caused either by somatic mutations, or genomic duplications of regions that include this gene, have been associated with hyperplasias and adenomas of the adrenal cortex and are linked to corticotropin-independent Cushing's syndrome. Alternative splicing results in multiple transcript variants encoding different isoforms. Tissue-specific isoforms that differ at the N-terminus have been described, and these isoforms may differ in the post-translational modifications that occur at the N-terminus of some isoforms. [provided by RefSeq, Jan 2015]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -11 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.73).
BP6
?
Variant 19-14102831-G-C is Benign according to our data. Variant chr19-14102831-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 2649414.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=-0.818 with no splicing effect.
BS2
?
High AC in GnomAd at 15 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PRKACA | NM_002730.4 | c.321C>G | p.Leu107= | synonymous_variant | 4/10 | ENST00000308677.9 | |
PRKACA | NM_001304349.2 | c.549C>G | p.Leu183= | synonymous_variant | 4/10 | ||
PRKACA | NM_207518.3 | c.297C>G | p.Leu99= | synonymous_variant | 4/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRKACA | ENST00000308677.9 | c.321C>G | p.Leu107= | synonymous_variant | 4/10 | 1 | NM_002730.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000986 AC: 15AN: 152204Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000557 AC: 14AN: 251486Hom.: 0 AF XY: 0.0000441 AC XY: 6AN XY: 135918
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GnomAD4 exome AF: 0.0000965 AC: 141AN: 1461718Hom.: 0 Cov.: 31 AF XY: 0.0000894 AC XY: 65AN XY: 727180
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GnomAD4 genome ? AF: 0.0000985 AC: 15AN: 152322Hom.: 0 Cov.: 32 AF XY: 0.0000940 AC XY: 7AN XY: 74484
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jul 01, 2022 | PRKACA: BP4, BP7 - |
Computational scores
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Name
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Benign
Cadd
Benign
Dann
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at