rs16859382

Variant names:

• chr2-218829133-T-C
• rs16859382
• NM_017431.4:c.634-533A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 11 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=-0.99).
• 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 rank	MANE	Protein	UniProt
PRKAG3	NM_017431.4	c.634-533A>G		intron_variant	Intron 4 of 13	ENST00000439262.7	NP_059127.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKAG3	ENST00000439262.7	c.634-533A>G		intron_variant	Intron 4 of 13	1	NM_017431.4	ENSP00000397133.3
PRKAG3	ENST00000529249.6	c.634-533A>G		intron_variant	Intron 4 of 12	1		ENSP00000436068.1
PRKAG3	ENST00000470307.6	n.634-533A>G		intron_variant	Intron 4 of 10	5		ENSP00000419272.2
PRKAG3	ENST00000490971.1	n.667-533A>G		intron_variant	Intron 4 of 8	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

African (AFR) AF: 0.632 AC: 26165 AN: 41432

American (AMR) AF: 0.0775 AC: 1183 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.0150 AC: 52 AN: 3470

East Asian (EAS) AF: 0.00849 AC: 44 AN: 5184

South Asian (SAS) AF: 0.00851 AC: 41 AN: 4820

European-Finnish (FIN) AF: 0.000283 AC: 3 AN: 10614

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.00353 AC: 240 AN: 68008

Other (OTH) AF: 0.138 AC: 292 AN: 2114

Alfa AF: 0.0611 Hom.: 4236

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
PhyloP100		0.16
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs16859382; hg19: chr2-219693856;