5-40795766-C-T

Position:

• chr5-40795766-C-T

Variant summary

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

The NM_006251.6(PRKAA1):​c.127+2297G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.695 in 152,166 control chromosomes in the GnomAD database, including 36,828 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 0.70 (36828 hom., cov: 34)
• Consequence: PRKAA1 NM_006251.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.718

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=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.781 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRKAA1	NM_006251.6	c.127+2297G>A		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+2297G>A		intron_variant		1	NM_006251.6	ENSP00000380317	P1

Frequencies

GnomAD3 genomes AF: 0.695 AC: 105699 AN: 152048 Hom.: 36802 Cov.: 34

Gnomad AFR AF: 0.654

Gnomad AMI AF: 0.696

Gnomad AMR AF: 0.750

Gnomad ASJ AF: 0.658

Gnomad EAS AF: 0.801

Gnomad SAS AF: 0.709

Gnomad FIN AF: 0.690

Gnomad MID AF: 0.595

Gnomad NFE AF: 0.703

Gnomad OTH AF: 0.668

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

GnomAD4 genome AF: 0.695 AC: 105776 AN: 152166 Hom.: 36828 Cov.: 34 AF XY: 0.698 AC XY: 51907 AN XY: 74396

Gnomad4 AFR AF: 0.654

Gnomad4 AMR AF: 0.750

Gnomad4 ASJ AF: 0.658

Gnomad4 EAS AF: 0.801

Gnomad4 SAS AF: 0.711

Gnomad4 FIN AF: 0.690

Gnomad4 NFE AF: 0.703

Gnomad4 OTH AF: 0.662

Alfa AF: 0.699 Hom.: 5487

Bravo AF: 0.695

Asia WGS AF: 0.705 AC: 2453 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	9.8
DANN	Benign	0.50

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: rs154268; hg19: chr5-40795868;