2-218824243-G-A
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Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BS1BS2
The NM_017431.4(PRKAG3):c.1332C>T(p.Ile444=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00152 in 1,614,104 control chromosomes in the GnomAD database, including 30 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0085 ( 14 hom., cov: 32)
Exomes 𝑓: 0.00080 ( 16 hom. )
Consequence
PRKAG3
NM_017431.4 synonymous
NM_017431.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.0640
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 -13 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.39).
BP6
Variant 2-218824243-G-A is Benign according to our data. Variant chr2-218824243-G-A is described in ClinVar as [Benign]. Clinvar id is 3041308.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=0.064 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00847 (1289/152234) while in subpopulation AFR AF= 0.03 (1248/41538). AF 95% confidence interval is 0.0287. There are 14 homozygotes in gnomad4. There are 598 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High AC in GnomAd4 at 1289 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PRKAG3 | NM_017431.4 | c.1332C>T | p.Ile444= | synonymous_variant | 12/14 | ENST00000439262.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRKAG3 | ENST00000439262.7 | c.1332C>T | p.Ile444= | synonymous_variant | 12/14 | 1 | NM_017431.4 | P1 | |
PRKAG3 | ENST00000529249.5 | c.1332C>T | p.Ile444= | synonymous_variant | 12/13 | 1 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00841 AC: 1280AN: 152116Hom.: 14 Cov.: 32
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GnomAD3 exomes AF: 0.00216 AC: 542AN: 251174Hom.: 8 AF XY: 0.00153 AC XY: 208AN XY: 135764
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GnomAD4 exome AF: 0.000796 AC: 1164AN: 1461870Hom.: 16 Cov.: 33 AF XY: 0.000645 AC XY: 469AN XY: 727234
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GnomAD4 genome AF: 0.00847 AC: 1289AN: 152234Hom.: 14 Cov.: 32 AF XY: 0.00804 AC XY: 598AN XY: 74416
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
PRKAG3-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Nov 11, 2019 | This variant is classified as 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
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at