NM_006251.6:c.127+7614C>T

Variant names:

• chr5-40790449-G-A
• rs10074991
• NM_006251.6:c.127+7614C>T

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+7614C>T 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 151,680 control chromosomes in the GnomAD database, including 7,709 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 (7709 hom., cov: 31)
• Consequence: PRKAA1 NM_006251.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.216
• Publications: 41 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]

ENSG00000212567 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.539 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006251.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKAA1	NM_006251.6	MANE Select	c.127+7614C>T		intron	N/A	NP_006242.5
	PRKAA1	NM_206907.4		c.127+7614C>T		intron	N/A	NP_996790.3
	PRKAA1	NM_001355028.2		c.-258+7614C>T		intron	N/A	NP_001341957.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKAA1	ENST00000397128.7	TSL:1 MANE Select	c.127+7614C>T		intron	N/A	ENSP00000380317.2
	PRKAA1	ENST00000354209.7	TSL:1	c.127+7614C>T		intron	N/A	ENSP00000346148.3
	PRKAA1	ENST00000296800.4	TSL:1	c.100+7614C>T		intron	N/A	ENSP00000296800.4

Frequencies

GnomAD3 genomes AF: 0.314 AC: 47596 AN: 151570 Hom.: 7705 Cov.: 31

Gnomad AFR AF: 0.359

Gnomad AMI AF: 0.307

Gnomad AMR AF: 0.278

Gnomad ASJ AF: 0.362

Gnomad EAS AF: 0.555

Gnomad SAS AF: 0.336

Gnomad FIN AF: 0.294

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.276

Gnomad OTH AF: 0.305

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

GnomAD4 genome AF: 0.314 AC: 47619 AN: 151680 Hom.: 7709 Cov.: 31 AF XY: 0.316 AC XY: 23416 AN XY: 74114

African (AFR) AF: 0.358 AC: 14794 AN: 41316

American (AMR) AF: 0.278 AC: 4230 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.362 AC: 1257 AN: 3470

East Asian (EAS) AF: 0.556 AC: 2855 AN: 5136

South Asian (SAS) AF: 0.339 AC: 1633 AN: 4818

European-Finnish (FIN) AF: 0.294 AC: 3083 AN: 10474

Middle Eastern (MID) AF: 0.325 AC: 95 AN: 292

European-Non Finnish (NFE) AF: 0.276 AC: 18757 AN: 67928

Other (OTH) AF: 0.302 AC: 635 AN: 2100

Alfa AF: 0.286 Hom.: 9303

Bravo AF: 0.313

Asia WGS AF: 0.370 AC: 1284 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.052
DANN	Benign	0.39
PhyloP100		-0.22
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: rs10074991; hg19: chr5-40790551;