rs1342382

Positions:

• chr1-56711715-T-A

Variant summary

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

The NM_006252.4(PRKAA2):​c.*4002T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.128 in 152,134 control chromosomes in the GnomAD database, including 2,030 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 0.13 (2030 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: PRKAA2 NM_006252.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.993

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=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.27 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRKAA2	NM_006252.4	c.*4002T>A		3_prime_UTR_variant	9/9	ENST00000371244.9	NP_006243.2
PRKAA2	XM_017001693.2	c.*4002T>A		3_prime_UTR_variant	9/9		XP_016857182.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRKAA2	ENST00000371244.9	c.*4002T>A		3_prime_UTR_variant	9/9	1	NM_006252.4	ENSP00000360290.4

Frequencies

GnomAD3 genomes AF: 0.128 AC: 19496 AN: 152016 Hom.: 2022 Cov.: 32

Gnomad AFR AF: 0.274

Gnomad AMI AF: 0.0746

Gnomad AMR AF: 0.0786

Gnomad ASJ AF: 0.0507

Gnomad EAS AF: 0.240

Gnomad SAS AF: 0.211

Gnomad FIN AF: 0.0736

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0503

Gnomad OTH AF: 0.118

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.128 AC: 19543 AN: 152134 Hom.: 2030 Cov.: 32 AF XY: 0.130 AC XY: 9675 AN XY: 74374

Gnomad4 AFR AF: 0.274

Gnomad4 AMR AF: 0.0788

Gnomad4 ASJ AF: 0.0507

Gnomad4 EAS AF: 0.240

Gnomad4 SAS AF: 0.210

Gnomad4 FIN AF: 0.0736

Gnomad4 NFE AF: 0.0503

Gnomad4 OTH AF: 0.118

Alfa AF: 0.0918 Hom.: 155

Bravo AF: 0.134

Asia WGS AF: 0.231 AC: 799 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	8.7
DANN	Benign	0.83

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: rs1342382; hg19: chr1-57177388;