rs6436094

Positions:

• chr2-218822874-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000439262.7(PRKAG3):​c.*319T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.292 in 984,546 control chromosomes in the GnomAD database, including 52,504 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.43 (19206 hom., cov: 32)
  • Exomes 𝑓: 0.27 (33298 hom.)
• Consequence: PRKAG3 ENST00000439262.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.491

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.833 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRKAG3	NM_017431.4	c.*319T>C		3_prime_UTR_variant	14/14	ENST00000439262.7	NP_059127.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRKAG3	ENST00000439262.7	c.*319T>C		3_prime_UTR_variant	14/14	1	NM_017431.4	ENSP00000397133	P1

Frequencies

GnomAD3 genomes AF: 0.427 AC: 64988 AN: 152022 Hom.: 19146 Cov.: 32

Gnomad AFR AF: 0.840

Gnomad AMI AF: 0.207

Gnomad AMR AF: 0.328

Gnomad ASJ AF: 0.430

Gnomad EAS AF: 0.505

Gnomad SAS AF: 0.277

Gnomad FIN AF: 0.168

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.248

Gnomad OTH AF: 0.391

GnomAD4 exome AF: 0.267 AC: 221931 AN: 832406 Hom.: 33298 Cov.: 29 AF XY: 0.266 AC XY: 102317 AN XY: 384458

Gnomad4 AFR exome AF: 0.891

Gnomad4 AMR exome AF: 0.301

Gnomad4 ASJ exome AF: 0.416

Gnomad4 EAS exome AF: 0.543

Gnomad4 SAS exome AF: 0.280

Gnomad4 FIN exome AF: 0.150

Gnomad4 NFE exome AF: 0.249

Gnomad4 OTH exome AF: 0.310

GnomAD4 genome AF: 0.428 AC: 65102 AN: 152140 Hom.: 19206 Cov.: 32 AF XY: 0.421 AC XY: 31337 AN XY: 74386

Gnomad4 AFR AF: 0.840

Gnomad4 AMR AF: 0.328

Gnomad4 ASJ AF: 0.430

Gnomad4 EAS AF: 0.505

Gnomad4 SAS AF: 0.276

Gnomad4 FIN AF: 0.168

Gnomad4 NFE AF: 0.248

Gnomad4 OTH AF: 0.393

Alfa AF: 0.281 Hom.: 5278

Bravo AF: 0.459

Asia WGS AF: 0.425 AC: 1477 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.88
DANN	Benign	0.57

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs6436094; hg19: chr2-219687597;