rs3805486

Positions:

• chr5-40795943-A-G
• chr5-40795943-A-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+2120T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.16 in 152,248 control chromosomes in the GnomAD database, including 2,041 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 (2041 hom., cov: 32)
• Consequence: PRKAA1 NM_006251.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.69

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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.24 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRKAA1	NM_006251.6	c.127+2120T>C		intron_variant		ENST00000397128.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKAA1	ENST00000397128.7	c.127+2120T>C		intron_variant		1	NM_006251.6	P1

Frequencies

GnomAD3 genomes AF: 0.160 AC: 24372 AN: 152130 Hom.: 2038 Cov.: 32

Gnomad AFR AF: 0.195

Gnomad AMI AF: 0.154

Gnomad AMR AF: 0.152

Gnomad ASJ AF: 0.167

Gnomad EAS AF: 0.251

Gnomad SAS AF: 0.134

Gnomad FIN AF: 0.128

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.141

Gnomad OTH AF: 0.174

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

GnomAD4 genome AF: 0.160 AC: 24391 AN: 152248 Hom.: 2041 Cov.: 32 AF XY: 0.159 AC XY: 11819 AN XY: 74436

Gnomad4 AFR AF: 0.195

Gnomad4 AMR AF: 0.151

Gnomad4 ASJ AF: 0.167

Gnomad4 EAS AF: 0.251

Gnomad4 SAS AF: 0.136

Gnomad4 FIN AF: 0.128

Gnomad4 NFE AF: 0.141

Gnomad4 OTH AF: 0.171

Alfa AF: 0.143 Hom.: 2576

Bravo AF: 0.165

Asia WGS AF: 0.184 AC: 641 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	9.3
DANN	Benign	0.66

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: rs3805486; hg19: chr5-40796045;