NM_006251.6:c.128-5833G>T

Variant names:

• chr5-40783419-C-A
• rs13167906
• NM_006251.6:c.128-5833G>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.128-5833G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 152,002 control chromosomes in the GnomAD database, including 2,683 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 0.16 (2683 hom., cov: 32)
• Consequence: PRKAA1 NM_006251.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.511
• Publications: 3 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]

ENSG00000300383 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.236 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKAA1	NM_006251.6	c.128-5833G>T		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.128-5833G>T		intron_variant	Intron 1 of 8	1	NM_006251.6	ENSP00000380317.2

Frequencies

GnomAD3 genomes AF: 0.164 AC: 24950 AN: 151884 Hom.: 2685 Cov.: 32

Gnomad AFR AF: 0.0409

Gnomad AMI AF: 0.274

Gnomad AMR AF: 0.162

Gnomad ASJ AF: 0.247

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.112

Gnomad FIN AF: 0.228

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.239

Gnomad OTH AF: 0.199

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

GnomAD4 genome AF: 0.164 AC: 24931 AN: 152002 Hom.: 2683 Cov.: 32 AF XY: 0.162 AC XY: 12056 AN XY: 74278

African (AFR) AF: 0.0408 AC: 1692 AN: 41486

American (AMR) AF: 0.162 AC: 2467 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.247 AC: 855 AN: 3466

East Asian (EAS) AF: 0.00174 AC: 9 AN: 5186

South Asian (SAS) AF: 0.110 AC: 532 AN: 4822

European-Finnish (FIN) AF: 0.228 AC: 2393 AN: 10514

Middle Eastern (MID) AF: 0.272 AC: 80 AN: 294

European-Non Finnish (NFE) AF: 0.239 AC: 16236 AN: 67948

Other (OTH) AF: 0.197 AC: 417 AN: 2112

Alfa AF: 0.0967 Hom.: 155

Bravo AF: 0.155

Asia WGS AF: 0.0510 AC: 177 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.5
DANN	Benign	0.53
PhyloP100		-0.51
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: rs13167906; hg19: chr5-40783521;