NM_006251.6:c.127+6281G>A

Variant names:

• chr5-40791782-C-T
• rs13361707
• NM_006251.6:c.127+6281G>A

Variant summary

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

The NM_006251.6(PRKAA1):​c.127+6281G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.314 in 152,020 control chromosomes in the GnomAD database, including 7,726 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 0.31 (7726 hom., cov: 32)
• Consequence: PRKAA1 NM_006251.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0840
• Publications: 83 publications found

Genes affected

PRKAA1 (HGNC:9376): (protein kinase AMP-activated catalytic subunit alpha 1) The protein encoded by this gene belongs to the ser/thr protein kinase family. It is the catalytic subunit of the 5'-prime-AMP-activated protein kinase (AMPK). AMPK is a cellular energy sensor conserved in all eukaryotic cells. The kinase activity of AMPK is activated by the stimuli that increase the cellular AMP/ATP ratio. AMPK regulates the activities of a number of key metabolic enzymes through phosphorylation. It protects cells from stresses that cause ATP depletion by switching off ATP-consuming biosynthetic pathways. Alternatively spliced transcript variants encoding distinct isoforms have been observed. [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=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.538 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKAA1	NM_006251.6	c.127+6281G>A		intron_variant	Intron 1 of 8	ENST00000397128.7	NP_006242.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKAA1	ENST00000397128.7	c.127+6281G>A		intron_variant	Intron 1 of 8	1	NM_006251.6	ENSP00000380317.2

Frequencies

GnomAD3 genomes AF: 0.314 AC: 47709 AN: 151902 Hom.: 7722 Cov.: 32

Gnomad AFR AF: 0.359

Gnomad AMI AF: 0.308

Gnomad AMR AF: 0.277

Gnomad ASJ AF: 0.363

Gnomad EAS AF: 0.555

Gnomad SAS AF: 0.335

Gnomad FIN AF: 0.296

Gnomad MID AF: 0.315

Gnomad NFE AF: 0.276

Gnomad OTH AF: 0.304

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

GnomAD4 genome AF: 0.314 AC: 47732 AN: 152020 Hom.: 7726 Cov.: 32 AF XY: 0.316 AC XY: 23478 AN XY: 74294

African (AFR) AF: 0.358 AC: 14841 AN: 41458

American (AMR) AF: 0.277 AC: 4227 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.363 AC: 1258 AN: 3468

East Asian (EAS) AF: 0.555 AC: 2870 AN: 5168

South Asian (SAS) AF: 0.338 AC: 1628 AN: 4816

European-Finnish (FIN) AF: 0.296 AC: 3124 AN: 10564

Middle Eastern (MID) AF: 0.318 AC: 93 AN: 292

European-Non Finnish (NFE) AF: 0.276 AC: 18774 AN: 67966

Other (OTH) AF: 0.302 AC: 637 AN: 2108

Alfa AF: 0.290 Hom.: 18959

Bravo AF: 0.313

Asia WGS AF: 0.370 AC: 1284 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	12
DANN	Benign	0.73
PhyloP100		-0.084
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: rs13361707; hg19: chr5-40791884;