chr2-218827079-G-A
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2
The NM_017431.4(PRKAG3):c.1017C>T(p.Pro339=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000288 in 1,613,182 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 0.00022 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00030 ( 0 hom. )
Consequence
PRKAG3
NM_017431.4 synonymous
NM_017431.4 synonymous
Scores
1
1
Clinical Significance
Conservation
PhyloP100: 0.0250
Genes affected
PRKAG3 (HGNC:9387): (protein kinase AMP-activated non-catalytic subunit gamma 3) The protein encoded by this gene is a regulatory subunit of the AMP-activated protein kinase (AMPK). AMPK is a heterotrimer consisting of an alpha catalytic subunit, and non-catalytic beta and gamma subunits. AMPK is an important energy-sensing enzyme that monitors cellular energy status. In response to cellular metabolic stresses, AMPK is activated, and thus phosphorylates and inactivates acetyl-CoA carboxylase (ACC) and beta-hydroxy beta-methylglutaryl-CoA reductase (HMGCR), key enzymes involved in regulating de novo biosynthesis of fatty acid and cholesterol. This subunit is one of the gamma regulatory subunits of AMPK. It is dominantly expressed in skeletal muscle. Studies of the pig counterpart suggest that this subunit may play a key role in the regulation of energy metabolism in skeletal muscle. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -15 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.43).
BP6
?
Variant 2-218827079-G-A is Benign according to our data. Variant chr2-218827079-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2651899.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=0.025 with no splicing effect.
BS2
?
High AC in GnomAd at 33 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PRKAG3 | NM_017431.4 | c.1017C>T | p.Pro339= | synonymous_variant | 10/14 | ENST00000439262.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRKAG3 | ENST00000439262.7 | c.1017C>T | p.Pro339= | synonymous_variant | 10/14 | 1 | NM_017431.4 | P1 | |
PRKAG3 | ENST00000529249.5 | c.1017C>T | p.Pro339= | synonymous_variant | 10/13 | 1 | P1 | ||
PRKAG3 | ENST00000490971.1 | n.1175C>T | non_coding_transcript_exon_variant | 9/9 | 2 | ||||
PRKAG3 | ENST00000470307.6 | c.971C>T | p.Pro324Leu | missense_variant, NMD_transcript_variant | 9/11 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.000217 AC: 33AN: 152208Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000191 AC: 48AN: 251458Hom.: 0 AF XY: 0.000213 AC XY: 29AN XY: 135906
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GnomAD4 exome AF: 0.000296 AC: 432AN: 1460974Hom.: 0 Cov.: 34 AF XY: 0.000286 AC XY: 208AN XY: 726794
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Oct 01, 2022 | PRKAG3: BP4, BP7 - |
PRKAG3-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jun 30, 2023 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
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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