NM_006251.6:c.821+171T>C

Variant names:

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

Variant summary

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

The NM_006251.6(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 NM_006251.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.319

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]

LOC124900968 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKAA1	NM_006251.6	c.821+171T>C		intron_variant	Intron 6 of 8	ENST00000397128.7	NP_006242.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKAA1	ENST00000397128.7	c.821+171T>C		intron_variant	Intron 6 of 8	1	NM_006251.6	ENSP00000380317.2

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

Gnomad4 AFR AF: 0.349

Gnomad4 AMR AF: 0.277

Gnomad4 ASJ AF: 0.370

Gnomad4 EAS AF: 0.557

Gnomad4 SAS AF: 0.340

Gnomad4 FIN AF: 0.295

Gnomad4 NFE AF: 0.276

Gnomad4 OTH AF: 0.301

Alfa AF: 0.284 Hom.: 11371

Bravo AF: 0.311

Asia WGS AF: 0.369 AC: 1281 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.9
DANN	Benign	0.52

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: rs1002424; hg19: chr5-40767397;