rs857148

chr1-56709485-A-Cchr1-56709485-A-T

Variant summary

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

The NM_006252.4(PRKAA2):c.*1772A>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 0.44 in 151,936 control chromosomes in the GnomAD database, including 15,427 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 0.44 (15426 hom., cov: 32)
  • Exomes 𝑓: 0.75 (1 hom.)
• Consequence: PRKAA2 NM_006252.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.316

Genes affected

PRKAA2 (HGNC:9377): (protein kinase AMP-activated catalytic subunit alpha 2) The protein encoded by this gene is a catalytic 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. Studies of the mouse counterpart suggest that this catalytic subunit may control whole-body insulin sensitivity and is necessary for maintaining myocardial energy homeostasis during ischemia. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.573 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRKAA2	NM_006252.4	c.*1772A>C		3_prime_UTR_variant	9/9	ENST00000371244.9
PRKAA2	XM_017001693.2	c.*1772A>C		3_prime_UTR_variant	9/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKAA2	ENST00000371244.9	c.*1772A>C		3_prime_UTR_variant	9/9	1	NM_006252.4	P1

Frequencies

GnomAD3 genomes AF: 0.441 AC: 66875 AN: 151814 Hom.: 15406 Cov.: 32

Gnomad AFR AF: 0.316

Gnomad AMI AF: 0.396

Gnomad AMR AF: 0.574

Gnomad ASJ AF: 0.430

Gnomad EAS AF: 0.592

Gnomad SAS AF: 0.552

Gnomad FIN AF: 0.470

Gnomad MID AF: 0.399

Gnomad NFE AF: 0.464

Gnomad OTH AF: 0.429

GnomAD4 exome AF: 0.750 AC: 3 AN: 4 Hom.: 1 Cov.: 0 AC XY: 0 AN XY: 0

Gnomad4 NFE exome AF: 0.750

GnomAD4 genome AF: 0.440 AC: 66914 AN: 151932 Hom.: 15426 Cov.: 32 AF XY: 0.446 AC XY: 33083 AN XY: 74254

Gnomad4 AFR AF: 0.316

Gnomad4 AMR AF: 0.574

Gnomad4 ASJ AF: 0.430

Gnomad4 EAS AF: 0.591

Gnomad4 SAS AF: 0.552

Gnomad4 FIN AF: 0.470

Gnomad4 NFE AF: 0.464

Gnomad4 OTH AF: 0.433

Alfa AF: 0.462 Hom.: 27278

Bravo AF: 0.442

Asia WGS AF: 0.538 AC: 1872 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
Cadd	Benign	12
Dann	Benign	0.82

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: rs857148; hg19: chr1-57175158;