5-40767295-A-G

Variant names:

• chr5-40767295-A-G
• rs1002424
• NM_006251.6:c.821+171T>C

Variant summary

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

The ENST00000397128.7(PRKAA1):​c.821+171T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.311 in 152,082 control chromosomes in the GnomAD database, including 7,618 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 0.31 (7618 hom., cov: 32)
• Consequence: PRKAA1 ENST00000397128.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.319
• Publications: 17 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.54 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000397128.7. 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.821+171T>C		intron	N/A	NP_006242.5
	PRKAA1	NM_206907.4		c.866+171T>C		intron	N/A	NP_996790.3
	PRKAA1	NM_001355028.2		c.743+171T>C		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.821+171T>C		intron	N/A	ENSP00000380317.2
	PRKAA1	ENST00000354209.7	TSL:1	c.866+171T>C		intron	N/A	ENSP00000346148.3
	PRKAA1	ENST00000505783.5	TSL:2	n.450+171T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.312 AC: 47342 AN: 151964 Hom.: 7613 Cov.: 32

Gnomad AFR AF: 0.350

Gnomad AMI AF: 0.307

Gnomad AMR AF: 0.277

Gnomad ASJ AF: 0.370

Gnomad EAS AF: 0.556

Gnomad SAS AF: 0.338

Gnomad FIN AF: 0.295

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.275

Gnomad OTH AF: 0.303

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

GnomAD4 genome AF: 0.311 AC: 47363 AN: 152082 Hom.: 7618 Cov.: 32 AF XY: 0.313 AC XY: 23305 AN XY: 74358

African (AFR) AF: 0.349 AC: 14470 AN: 41472

American (AMR) AF: 0.277 AC: 4235 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.370 AC: 1284 AN: 3468

East Asian (EAS) AF: 0.557 AC: 2878 AN: 5170

South Asian (SAS) AF: 0.340 AC: 1642 AN: 4828

European-Finnish (FIN) AF: 0.295 AC: 3112 AN: 10564

Middle Eastern (MID) AF: 0.330 AC: 97 AN: 294

European-Non Finnish (NFE) AF: 0.276 AC: 18731 AN: 67982

Other (OTH) AF: 0.301 AC: 634 AN: 2106

Alfa AF: 0.287 Hom.: 17888

Bravo AF: 0.311

Asia WGS AF: 0.369 AC: 1281 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.9
DANN	Benign	0.52
PhyloP100		0.32
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: rs1002424; hg19: chr5-40767397;