5-40782137-C-T

Variant names:

• chr5-40782137-C-T
• rs249429
• NM_006251.6:c.128-4551G>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.128-4551G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.705 in 151,866 control chromosomes in the GnomAD database, including 37,806 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 0.71 (37806 hom., cov: 31)
• Consequence: PRKAA1 NM_006251.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.443
• Publications: 8 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]

LOC124900968 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.781 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKAA1	NM_006251.6	MANE Select	c.128-4551G>A		intron	N/A	NP_006242.5
	PRKAA1	NM_206907.4		c.128-4551G>A		intron	N/A	NP_996790.3
	PRKAA1	NM_001355028.2		c.-257-1799G>A		intron	N/A	NP_001341957.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKAA1	ENST00000397128.7	TSL:1 MANE Select	c.128-4551G>A		intron	N/A	ENSP00000380317.2	Q13131-1
	PRKAA1	ENST00000354209.7	TSL:1	c.128-4551G>A		intron	N/A	ENSP00000346148.3	Q13131-2
	PRKAA1	ENST00000296800.4	TSL:1	c.101-4551G>A		intron	N/A	ENSP00000296800.4	Q96E92

Frequencies

GnomAD3 genomes AF: 0.705 AC: 107004 AN: 151748 Hom.: 37772 Cov.: 31

Gnomad AFR AF: 0.687

Gnomad AMI AF: 0.696

Gnomad AMR AF: 0.761

Gnomad ASJ AF: 0.657

Gnomad EAS AF: 0.801

Gnomad SAS AF: 0.708

Gnomad FIN AF: 0.688

Gnomad MID AF: 0.604

Gnomad NFE AF: 0.703

Gnomad OTH AF: 0.681

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

GnomAD4 genome AF: 0.705 AC: 107093 AN: 151866 Hom.: 37806 Cov.: 31 AF XY: 0.708 AC XY: 52516 AN XY: 74196

African (AFR) AF: 0.686 AC: 28417 AN: 41398

American (AMR) AF: 0.761 AC: 11604 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.657 AC: 2280 AN: 3468

East Asian (EAS) AF: 0.801 AC: 4136 AN: 5162

South Asian (SAS) AF: 0.711 AC: 3424 AN: 4818

European-Finnish (FIN) AF: 0.688 AC: 7235 AN: 10516

Middle Eastern (MID) AF: 0.619 AC: 182 AN: 294

European-Non Finnish (NFE) AF: 0.703 AC: 47761 AN: 67942

Other (OTH) AF: 0.674 AC: 1422 AN: 2110

Alfa AF: 0.702 Hom.: 49678

Bravo AF: 0.708

Asia WGS AF: 0.710 AC: 2469 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	0.95
DANN	Benign	0.50
PhyloP100		-0.44
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: rs249429; hg19: chr5-40782239;