2-218831291-G-A

Variant names:

• chr2-218831291-G-A
• rs650898
• ENST00000439262.7:c.73+45C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000439262.7(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 ENST00000439262.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.574
• Publications: 9 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PRKAG3	NM_017431.4	c.73+45C>T		intron_variant	Intron 2 of 13		NP_059127.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKAG3	ENST00000439262.7	c.73+45C>T		intron_variant	Intron 2 of 13	1		ENSP00000397133.3

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

GnomAD2 exomes AF: 0.922 AC: 165775 AN: 179836 AF XY: 0.919

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 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

African (AFR) AF: 0.988 AC: 28928 AN: 29294

American (AMR) AF: 0.924 AC: 27473 AN: 29738

Ashkenazi Jewish (ASJ) AF: 0.926 AC: 19580 AN: 21140

East Asian (EAS) AF: 0.999 AC: 38195 AN: 38240

South Asian (SAS) AF: 0.903 AC: 64142 AN: 71016

European-Finnish (FIN) AF: 0.890 AC: 45099 AN: 50678

Middle Eastern (MID) AF: 0.915 AC: 4690 AN: 5128

European-Non Finnish (NFE) AF: 0.911 AC: 915065 AN: 1004166

Other (OTH) AF: 0.919 AC: 49952 AN: 54336

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

African (AFR) AF: 0.985 AC: 40882 AN: 41522

American (AMR) AF: 0.930 AC: 14230 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.920 AC: 3195 AN: 3472

East Asian (EAS) AF: 0.998 AC: 5156 AN: 5166

South Asian (SAS) AF: 0.906 AC: 4369 AN: 4822

European-Finnish (FIN) AF: 0.893 AC: 9484 AN: 10616

Middle Eastern (MID) AF: 0.912 AC: 268 AN: 294

European-Non Finnish (NFE) AF: 0.906 AC: 61584 AN: 67992

Other (OTH) AF: 0.927 AC: 1954 AN: 2108

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
PhyloP100		-0.57
PromoterAI		0.037	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs650898; hg19: chr2-219696014;