rs650898

chr2-218831291-G-Achr2-218831291-G-Cchr2-218831291-G-T

Variant summary

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

The NM_017431.4(PRKAG3):c.73+45C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.917 in 1,455,936 control chromosomes in the GnomAD database, including 612,819 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 0.93 (66361 hom., cov: 30)
  • Exomes 𝑓: 0.92 (546458 hom.)
• Consequence: PRKAG3 NM_017431.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.574

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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRKAG3	NM_017431.4	c.73+45C>T		intron_variant		ENST00000439262.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKAG3	ENST00000439262.7	c.73+45C>T		intron_variant		1	NM_017431.4	P1

Frequencies

GnomAD3 genomes AF: 0.933 AC: 141878 AN: 152082 Hom.: 66304 Cov.: 30

Gnomad AFR AF: 0.985

Gnomad AMI AF: 0.959

Gnomad AMR AF: 0.930

Gnomad ASJ AF: 0.920

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.906

Gnomad FIN AF: 0.893

Gnomad MID AF: 0.911

Gnomad NFE AF: 0.906

Gnomad OTH AF: 0.926

GnomAD3 exomes AF: 0.922 AC: 165775 AN: 179836 Hom.: 76555 AF XY: 0.919 AC XY: 87614 AN XY: 95362

Gnomad AFR exome AF: 0.987

Gnomad AMR exome AF: 0.925

Gnomad ASJ exome AF: 0.923

Gnomad EAS exome AF: 0.999

Gnomad SAS exome AF: 0.906

Gnomad FIN exome AF: 0.890

Gnomad NFE exome AF: 0.906

Gnomad OTH exome AF: 0.924

GnomAD4 exome AF: 0.915 AC: 1193124 AN: 1303736 Hom.: 546458 Cov.: 21 AF XY: 0.915 AC XY: 589396 AN XY: 644384

Gnomad4 AFR exome AF: 0.988

Gnomad4 AMR exome AF: 0.924

Gnomad4 ASJ exome AF: 0.926

Gnomad4 EAS exome AF: 0.999

Gnomad4 SAS exome AF: 0.903

Gnomad4 FIN exome AF: 0.890

Gnomad4 NFE exome AF: 0.911

Gnomad4 OTH exome AF: 0.919

GnomAD4 genome AF: 0.933 AC: 141993 AN: 152200 Hom.: 66361 Cov.: 30 AF XY: 0.932 AC XY: 69376 AN XY: 74414

Gnomad4 AFR AF: 0.985

Gnomad4 AMR AF: 0.930

Gnomad4 ASJ AF: 0.920

Gnomad4 EAS AF: 0.998

Gnomad4 SAS AF: 0.906

Gnomad4 FIN AF: 0.893

Gnomad4 NFE AF: 0.906

Gnomad4 OTH AF: 0.927

Alfa AF: 0.908 Hom.: 16462

Bravo AF: 0.940

Asia WGS AF: 0.964 AC: 3349 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	3.6
Dann	Benign	0.81

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs650898; hg19: chr2-219696014;