rs16859382

chr2-218829133-T-C

Variant summary

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

The NM_017431.4(PRKAG3):c.634-533A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 152,120 control chromosomes in the GnomAD database, including 8,469 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 0.18 (8469 hom., cov: 32)
• Consequence: PRKAG3 NM_017431.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.159

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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.625 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRKAG3	NM_017431.4	c.634-533A>G		intron_variant		ENST00000439262.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKAG3	ENST00000439262.7	c.634-533A>G		intron_variant		1	NM_017431.4	P1
PRKAG3	ENST00000529249.5	c.634-533A>G		intron_variant		1		P1
PRKAG3	ENST00000470307.6	c.634-533A>G		intron_variant, NMD_transcript_variant		5
PRKAG3	ENST00000490971.1	n.667-533A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.184 AC: 27944 AN: 152002 Hom.: 8435 Cov.: 32

Gnomad AFR AF: 0.631

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0776

Gnomad ASJ AF: 0.0150

Gnomad EAS AF: 0.00847

Gnomad SAS AF: 0.00871

Gnomad FIN AF: 0.000283

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.00353

Gnomad OTH AF: 0.140

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.184 AC: 28037 AN: 152120 Hom.: 8469 Cov.: 32 AF XY: 0.179 AC XY: 13303 AN XY: 74378

Gnomad4 AFR AF: 0.632

Gnomad4 AMR AF: 0.0775

Gnomad4 ASJ AF: 0.0150

Gnomad4 EAS AF: 0.00849

Gnomad4 SAS AF: 0.00851

Gnomad4 FIN AF: 0.000283

Gnomad4 NFE AF: 0.00353

Gnomad4 OTH AF: 0.138

Alfa AF: 0.0237 Hom.: 1033

Asia WGS AF: 0.0540 AC: 190 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
Cadd	Benign	8.1
Dann	Benign	0.36

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: rs16859382; hg19: chr2-219693856;