1-56654080-T-A

Variant names:

• chr1-56654080-T-A
• rs10889007
• NM_006252.4:c.94+8599T>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006252.4(PRKAA2):​c.94+8599T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.786 in 151,878 control chromosomes in the GnomAD database, including 47,392 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 0.79 (47392 hom., cov: 30)
• Consequence: PRKAA2 NM_006252.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.162
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.831 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKAA2	NM_006252.4	c.94+8599T>A		intron_variant	Intron 1 of 8	ENST00000371244.9	NP_006243.2
PRKAA2	XM_017001693.2	c.-177+8085T>A		intron_variant	Intron 1 of 8		XP_016857182.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKAA2	ENST00000371244.9	c.94+8599T>A		intron_variant	Intron 1 of 8	1	NM_006252.4	ENSP00000360290.4

Frequencies

GnomAD3 genomes AF: 0.786 AC: 119247 AN: 151760 Hom.: 47366 Cov.: 30

Gnomad AFR AF: 0.716

Gnomad AMI AF: 0.817

Gnomad AMR AF: 0.830

Gnomad ASJ AF: 0.868

Gnomad EAS AF: 0.604

Gnomad SAS AF: 0.541

Gnomad FIN AF: 0.834

Gnomad MID AF: 0.804

Gnomad NFE AF: 0.837

Gnomad OTH AF: 0.803

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

GnomAD4 genome AF: 0.786 AC: 119324 AN: 151878 Hom.: 47392 Cov.: 30 AF XY: 0.781 AC XY: 57977 AN XY: 74234

African (AFR) AF: 0.715 AC: 29624 AN: 41412

American (AMR) AF: 0.830 AC: 12665 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.868 AC: 3010 AN: 3466

East Asian (EAS) AF: 0.605 AC: 3105 AN: 5136

South Asian (SAS) AF: 0.542 AC: 2608 AN: 4808

European-Finnish (FIN) AF: 0.834 AC: 8817 AN: 10572

Middle Eastern (MID) AF: 0.813 AC: 239 AN: 294

European-Non Finnish (NFE) AF: 0.837 AC: 56829 AN: 67904

Other (OTH) AF: 0.799 AC: 1682 AN: 2106

Alfa AF: 0.805 Hom.: 6127

Bravo AF: 0.788

Asia WGS AF: 0.618 AC: 2152 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.9
DANN	Benign	0.44
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: rs10889007; hg19: chr1-57119753;