rs13167906

chr5-40783419-C-Achr5-40783419-C-Gchr5-40783419-C-T

Variant summary

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

The NM_006251.6(PRKAA1):c.128-5833G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 152,002 control chromosomes in the GnomAD database, including 2,683 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 (2683 hom., cov: 32)
• Consequence: PRKAA1 NM_006251.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.511

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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.236 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRKAA1	NM_006251.6	c.128-5833G>T		intron_variant		ENST00000397128.7
LOC124900968	XR_007058747.1	n.1706+1810C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKAA1	ENST00000397128.7	c.128-5833G>T		intron_variant		1	NM_006251.6	P1

Frequencies

GnomAD3 genomes AF: 0.164 AC: 24950 AN: 151884 Hom.: 2685 Cov.: 32

Gnomad AFR AF: 0.0409

Gnomad AMI AF: 0.274

Gnomad AMR AF: 0.162

Gnomad ASJ AF: 0.247

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.112

Gnomad FIN AF: 0.228

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.239

Gnomad OTH AF: 0.199

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

GnomAD4 genome AF: 0.164 AC: 24931 AN: 152002 Hom.: 2683 Cov.: 32 AF XY: 0.162 AC XY: 12056 AN XY: 74278

Gnomad4 AFR AF: 0.0408

Gnomad4 AMR AF: 0.162

Gnomad4 ASJ AF: 0.247

Gnomad4 EAS AF: 0.00174

Gnomad4 SAS AF: 0.110

Gnomad4 FIN AF: 0.228

Gnomad4 NFE AF: 0.239

Gnomad4 OTH AF: 0.197

Alfa AF: 0.0967 Hom.: 155

Bravo AF: 0.155

Asia WGS AF: 0.0510 AC: 177 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	2.5
Dann	Benign	0.53

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: rs13167906; hg19: chr5-40783521;