5-40774942-C-A
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Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The ENST00000354209.7(PRKAA1):c.394G>T(p.Gly132Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000139 in 1,603,902 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00014 ( 1 hom. )
Consequence
PRKAA1
ENST00000354209.7 missense
ENST00000354209.7 missense
Scores
1
7
8
Clinical Significance
Conservation
PhyloP100: 1.95
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 -6 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.15928036).
BS2
High AC in GnomAd4 at 20 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PRKAA1 | NM_006251.6 | c.363+468G>T | intron_variant | ENST00000397128.7 | |||
LOC124900968 | XR_007058747.1 | n.1452-6413C>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRKAA1 | ENST00000397128.7 | c.363+468G>T | intron_variant | 1 | NM_006251.6 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000131 AC: 20AN: 152156Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000133 AC: 33AN: 247680Hom.: 1 AF XY: 0.000156 AC XY: 21AN XY: 134438
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GnomAD4 exome AF: 0.000140 AC: 203AN: 1451628Hom.: 1 Cov.: 29 AF XY: 0.000138 AC XY: 100AN XY: 722628
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GnomAD4 genome AF: 0.000131 AC: 20AN: 152274Hom.: 0 Cov.: 32 AF XY: 0.000161 AC XY: 12AN XY: 74458
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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 | Dec 06, 2021 | The c.394G>T (p.G132C) alteration is located in exon 4 (coding exon 4) of the PRKAA1 gene. This alteration results from a G to T substitution at nucleotide position 394, causing the glycine (G) at amino acid position 132 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Benign
D
LIST_S2
Benign
T
M_CAP
Pathogenic
D
MetaRNN
Benign
T
MetaSVM
Uncertain
T
MutationTaster
Benign
D;D;N
PrimateAI
Benign
T
PROVEAN
Benign
N
REVEL
Uncertain
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
P
Vest4
MVP
MPC
ClinPred
T
GERP RS
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