rs3805490

Positions:

• chr5-40792051-T-A
• chr5-40792051-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006251.6(PRKAA1):​c.127+6012A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.215 in 152,226 control chromosomes in the GnomAD database, including 4,348 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 0.21 (4348 hom., cov: 33)
• Consequence: PRKAA1 NM_006251.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.684

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.369 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRKAA1	NM_006251.6	c.127+6012A>T		intron_variant		ENST00000397128.7	NP_006242.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRKAA1	ENST00000397128.7	c.127+6012A>T		intron_variant		1	NM_006251.6	ENSP00000380317.2

Frequencies

GnomAD3 genomes AF: 0.215 AC: 32655 AN: 152108 Hom.: 4339 Cov.: 33

Gnomad AFR AF: 0.0793

Gnomad AMI AF: 0.183

Gnomad AMR AF: 0.376

Gnomad ASJ AF: 0.215

Gnomad EAS AF: 0.215

Gnomad SAS AF: 0.331

Gnomad FIN AF: 0.185

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.257

Gnomad OTH AF: 0.229

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

GnomAD4 genome AF: 0.215 AC: 32668 AN: 152226 Hom.: 4348 Cov.: 33 AF XY: 0.218 AC XY: 16207 AN XY: 74418

Gnomad4 AFR AF: 0.0791

Gnomad4 AMR AF: 0.377

Gnomad4 ASJ AF: 0.215

Gnomad4 EAS AF: 0.214

Gnomad4 SAS AF: 0.331

Gnomad4 FIN AF: 0.185

Gnomad4 NFE AF: 0.257

Gnomad4 OTH AF: 0.227

Alfa AF: 0.232 Hom.: 580

Bravo AF: 0.222

Asia WGS AF: 0.278 AC: 967 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.30
DANN	Benign	0.43

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

Publications

LitVar

Other links and lift over

dbSNP: rs3805490; hg19: chr5-40792153;