rs3738568

chr1-56707918-A-G

Variant summary

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

The NM_006252.4(PRKAA2):c.*205A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0367 in 597,550 control chromosomes in the GnomAD database, including 797 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 0.028 (115 hom., cov: 32)
  • Exomes 𝑓: 0.040 (682 hom.)
• Consequence: PRKAA2 NM_006252.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.71

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.113 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRKAA2	NM_006252.4	c.*205A>G		3_prime_UTR_variant	9/9	ENST00000371244.9
PRKAA2	XM_017001693.2	c.*205A>G		3_prime_UTR_variant	9/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKAA2	ENST00000371244.9	c.*205A>G		3_prime_UTR_variant	9/9	1	NM_006252.4	P1

Frequencies

GnomAD3 genomes AF: 0.0278 AC: 4229 AN: 152178 Hom.: 116 Cov.: 32

Gnomad AFR AF: 0.00586

Gnomad AMI AF: 0.0175

Gnomad AMR AF: 0.0222

Gnomad ASJ AF: 0.0317

Gnomad EAS AF: 0.121

Gnomad SAS AF: 0.0996

Gnomad FIN AF: 0.0438

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0278

Gnomad OTH AF: 0.0244

GnomAD4 exome AF: 0.0398 AC: 17723 AN: 445254 Hom.: 682 Cov.: 5 AF XY: 0.0422 AC XY: 9902 AN XY: 234646

Gnomad4 AFR exome AF: 0.00550

Gnomad4 AMR exome AF: 0.0120

Gnomad4 ASJ exome AF: 0.0319

Gnomad4 EAS exome AF: 0.135

Gnomad4 SAS exome AF: 0.0887

Gnomad4 FIN exome AF: 0.0383

Gnomad4 NFE exome AF: 0.0268

Gnomad4 OTH exome AF: 0.0305

GnomAD4 genome AF: 0.0278 AC: 4233 AN: 152296 Hom.: 115 Cov.: 32 AF XY: 0.0305 AC XY: 2269 AN XY: 74468

Gnomad4 AFR AF: 0.00585

Gnomad4 AMR AF: 0.0224

Gnomad4 ASJ AF: 0.0317

Gnomad4 EAS AF: 0.121

Gnomad4 SAS AF: 0.0995

Gnomad4 FIN AF: 0.0438

Gnomad4 NFE AF: 0.0278

Gnomad4 OTH AF: 0.0255

Alfa AF: 0.0245 Hom.: 28

Bravo AF: 0.0231

Asia WGS AF: 0.0920 AC: 320 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.10
Dann	Benign	0.61

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: rs3738568; hg19: chr1-57173591; COSMIC: COSV100983008;