5-40765164-A-G
Position:
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_006251.6(PRKAA1):āc.896T>Cā(p.Ile299Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,824 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: not found (cov: 32)
Exomes š: 0.0000048 ( 0 hom. )
Consequence
PRKAA1
NM_006251.6 missense
NM_006251.6 missense
Scores
4
12
3
Clinical Significance
Conservation
PhyloP100: 8.94
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 GnomAdExome4 at 7 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PRKAA1 | NM_006251.6 | c.896T>C | p.Ile299Thr | missense_variant | 7/9 | ENST00000397128.7 | NP_006242.5 | |
LOC124900968 | XR_007058747.1 | n.1451+697A>G | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PRKAA1 | ENST00000397128.7 | c.896T>C | p.Ile299Thr | missense_variant | 7/9 | 1 | NM_006251.6 | ENSP00000380317 | P1 | |
PRKAA1 | ENST00000354209.7 | c.941T>C | p.Ile314Thr | missense_variant | 8/10 | 1 | ENSP00000346148 | |||
PRKAA1 | ENST00000505783.5 | n.525T>C | non_coding_transcript_exon_variant | 4/4 | 2 | |||||
PRKAA1 | ENST00000506652.5 | n.855T>C | non_coding_transcript_exon_variant | 7/7 | 5 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD3 exomes AF: 0.00000401 AC: 1AN: 249414Hom.: 0 AF XY: 0.00000739 AC XY: 1AN XY: 135316
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GnomAD4 exome AF: 0.00000479 AC: 7AN: 1461824Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3AN XY: 727218
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GnomAD4 genome Cov.: 32
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32
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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 | Jun 17, 2024 | The c.941T>C (p.I314T) alteration is located in exon 8 (coding exon 8) of the PRKAA1 gene. This alteration results from a T to C substitution at nucleotide position 941, causing the isoleucine (I) at amino acid position 314 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Uncertain
D;.
Eigen
Uncertain
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
D;D
REVEL
Uncertain
Sift
Uncertain
D;D
Sift4G
Uncertain
D;D
Polyphen
P;P
Vest4
MVP
MPC
0.64
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
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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