rs11749437

Positions:

• chr5-40781925-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.128-4339A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.112 in 152,164 control chromosomes in the GnomAD database, including 1,310 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 0.11 (1310 hom., cov: 32)
• Consequence: PRKAA1 NM_006251.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.122

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 (NFE) allele frequency at 95% confidence interval = 0.165 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRKAA1	NM_006251.6	c.128-4339A>C		intron_variant		ENST00000397128.7	NP_006242.5
LOC124900968	XR_007058747.1	n.1706+316T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRKAA1	ENST00000397128.7	c.128-4339A>C		intron_variant		1	NM_006251.6	ENSP00000380317	P1

Frequencies

GnomAD3 genomes AF: 0.112 AC: 17044 AN: 152046 Hom.: 1311 Cov.: 32

Gnomad AFR AF: 0.0368

Gnomad AMI AF: 0.204

Gnomad AMR AF: 0.0735

Gnomad ASJ AF: 0.0793

Gnomad EAS AF: 0.00269

Gnomad SAS AF: 0.0381

Gnomad FIN AF: 0.204

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.167

Gnomad OTH AF: 0.0972

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

GnomAD4 genome AF: 0.112 AC: 17037 AN: 152164 Hom.: 1310 Cov.: 32 AF XY: 0.111 AC XY: 8222 AN XY: 74384

Gnomad4 AFR AF: 0.0367

Gnomad4 AMR AF: 0.0734

Gnomad4 ASJ AF: 0.0793

Gnomad4 EAS AF: 0.00270

Gnomad4 SAS AF: 0.0379

Gnomad4 FIN AF: 0.204

Gnomad4 NFE AF: 0.167

Gnomad4 OTH AF: 0.0957

Alfa AF: 0.137 Hom.: 637

Bravo AF: 0.0981

Asia WGS AF: 0.0340 AC: 120 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	7.0
DANN	Benign	0.59

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: rs11749437; hg19: chr5-40782027;