rs10053664

chr5-40785709-T-Cchr5-40785709-T-G

Variant summary

Our verdict is Benign. Variant got -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

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.454 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRKAA1	NM_006251.6	c.128-8123A>G		intron_variant		ENST00000397128.7
LOC124900968	XR_007058747.1	n.1706+4100T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKAA1	ENST00000397128.7	c.128-8123A>G		intron_variant		1	NM_006251.6	P1

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

Gnomad4 AFR AF: 0.233

Gnomad4 AMR AF: 0.463

Gnomad4 ASJ AF: 0.295

Gnomad4 EAS AF: 0.217

Gnomad4 SAS AF: 0.370

Gnomad4 FIN AF: 0.392

Gnomad4 NFE AF: 0.425

Gnomad4 OTH AF: 0.343

Alfa AF: 0.408 Hom.: 21423

Bravo AF: 0.360

Asia WGS AF: 0.320 AC: 1116 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	1.9
Dann	Benign	0.38

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

Publications

LitVar

Other links and lift over

dbSNP: rs10053664; hg19: chr5-40785811;