chr5-40798137-T-G
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_006251.6(PRKAA1):āc.53A>Cā(p.His18Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000136 in 1,605,056 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.000046 ( 0 hom., cov: 30)
Exomes š: 0.00015 ( 0 hom. )
Consequence
PRKAA1
NM_006251.6 missense
NM_006251.6 missense
Scores
2
6
11
Clinical Significance
Conservation
PhyloP100: 6.65
Genes affected
PRKAA1 (HGNC:9376): (protein kinase AMP-activated catalytic subunit alpha 1) The protein encoded by this gene belongs to the ser/thr protein kinase family. It is the catalytic subunit of the 5'-prime-AMP-activated protein kinase (AMPK). AMPK is a cellular energy sensor conserved in all eukaryotic cells. The kinase activity of AMPK is activated by the stimuli that increase the cellular AMP/ATP ratio. AMPK regulates the activities of a number of key metabolic enzymes through phosphorylation. It protects cells from stresses that cause ATP depletion by switching off ATP-consuming biosynthetic pathways. Alternatively spliced transcript variants encoding distinct isoforms have been observed. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
BS2
High AC in GnomAd4 at 7 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PRKAA1 | NM_006251.6 | c.53A>C | p.His18Pro | missense_variant | 1/9 | ENST00000397128.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRKAA1 | ENST00000397128.7 | c.53A>C | p.His18Pro | missense_variant | 1/9 | 1 | NM_006251.6 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000461 AC: 7AN: 151708Hom.: 0 Cov.: 30
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GnomAD3 exomes AF: 0.0000449 AC: 11AN: 245206Hom.: 0 AF XY: 0.0000525 AC XY: 7AN XY: 133254
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GnomAD4 exome AF: 0.000146 AC: 212AN: 1453348Hom.: 0 Cov.: 32 AF XY: 0.000140 AC XY: 101AN XY: 723234
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GnomAD4 genome AF: 0.0000461 AC: 7AN: 151708Hom.: 0 Cov.: 30 AF XY: 0.0000405 AC XY: 3AN XY: 74086
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 26, 2022 | The c.53A>C (p.H18P) alteration is located in exon 1 (coding exon 1) of the PRKAA1 gene. This alteration results from a A to C substitution at nucleotide position 53, causing the histidine (H) at amino acid position 18 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Benign
DEOGEN2
Benign
T;.;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Benign
D
LIST_S2
Uncertain
D;D;D
M_CAP
Pathogenic
D
MetaRNN
Uncertain
D;D;D
MetaSVM
Benign
T
MutationAssessor
Benign
N;N;.
MutationTaster
Benign
D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Benign
N;N;N
REVEL
Uncertain
Sift
Benign
T;T;T
Sift4G
Benign
T;T;T
Polyphen
P;P;.
Vest4
MVP
MPC
1.7
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at