5-40785709-T-C

Variant names:

• chr5-40785709-T-C
• rs10053664
• NM_006251.6:c.128-8123A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006251.6(PRKAA1):​c.128-8123A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.361 in 151,900 control chromosomes in the GnomAD database, including 10,705 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 0.36 (10705 hom., cov: 32)
• Consequence: PRKAA1 NM_006251.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0560
• Publications: 9 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.454 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKAA1	NM_006251.6	MANE Select	c.128-8123A>G		intron	N/A	NP_006242.5
	PRKAA1	NM_206907.4		c.128-8123A>G		intron	N/A	NP_996790.3
	PRKAA1	NM_001355028.2		c.-257-5371A>G		intron	N/A	NP_001341957.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKAA1	ENST00000397128.7	TSL:1 MANE Select	c.128-8123A>G		intron	N/A	ENSP00000380317.2
	PRKAA1	ENST00000354209.7	TSL:1	c.128-8123A>G		intron	N/A	ENSP00000346148.3
	PRKAA1	ENST00000296800.4	TSL:1	c.101-8123A>G		intron	N/A	ENSP00000296800.4

Frequencies

GnomAD3 genomes AF: 0.361 AC: 54779 AN: 151782 Hom.: 10696 Cov.: 32

Gnomad AFR AF: 0.233

Gnomad AMI AF: 0.389

Gnomad AMR AF: 0.462

Gnomad ASJ AF: 0.295

Gnomad EAS AF: 0.217

Gnomad SAS AF: 0.370

Gnomad FIN AF: 0.392

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.425

Gnomad OTH AF: 0.348

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

GnomAD4 genome AF: 0.361 AC: 54816 AN: 151900 Hom.: 10705 Cov.: 32 AF XY: 0.362 AC XY: 26837 AN XY: 74226

African (AFR) AF: 0.233 AC: 9671 AN: 41450

American (AMR) AF: 0.463 AC: 7060 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.295 AC: 1022 AN: 3470

East Asian (EAS) AF: 0.217 AC: 1123 AN: 5170

South Asian (SAS) AF: 0.370 AC: 1781 AN: 4816

European-Finnish (FIN) AF: 0.392 AC: 4103 AN: 10466

Middle Eastern (MID) AF: 0.286 AC: 84 AN: 294

European-Non Finnish (NFE) AF: 0.425 AC: 28891 AN: 67954

Other (OTH) AF: 0.343 AC: 726 AN: 2114

Alfa AF: 0.402 Hom.: 47935

Bravo AF: 0.360

Asia WGS AF: 0.320 AC: 1116 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.9
DANN	Benign	0.38
PhyloP100		0.056
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs10053664; hg19: chr5-40785811;