5-40781925-T-G

Variant names:

• chr5-40781925-T-G
• rs11749437
• NM_006251.6:c.128-4339A>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 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]

LOC124900968 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006251.6. 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.128-4339A>C		intron	N/A	NP_006242.5
	PRKAA1	NM_206907.4		c.128-4339A>C		intron	N/A	NP_996790.3
	PRKAA1	NM_001355028.2		c.-257-1587A>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.128-4339A>C		intron	N/A	ENSP00000380317.2
	PRKAA1	ENST00000354209.7	TSL:1	c.128-4339A>C		intron	N/A	ENSP00000346148.3
	PRKAA1	ENST00000296800.4	TSL:1	c.101-4339A>C		intron	N/A	ENSP00000296800.4

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

African (AFR) AF: 0.0367 AC: 1524 AN: 41546

American (AMR) AF: 0.0734 AC: 1121 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0793 AC: 275 AN: 3468

East Asian (EAS) AF: 0.00270 AC: 14 AN: 5184

South Asian (SAS) AF: 0.0379 AC: 183 AN: 4826

European-Finnish (FIN) AF: 0.204 AC: 2151 AN: 10552

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.167 AC: 11363 AN: 67994

Other (OTH) AF: 0.0957 AC: 202 AN: 2110

Alfa AF: 0.131 Hom.: 954

Bravo AF: 0.0981

Asia WGS AF: 0.0340 AC: 120 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	7.0
DANN	Benign	0.59
PhyloP100		0.12
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: rs11749437; hg19: chr5-40782027;