rs3805486

Variant names:

• chr5-40795943-A-G
• rs3805486
• NM_006251.6:c.127+2120T>C

Your query was ambiguous. Multiple possible variants found:

• chr5-40795943-A-G
• chr5-40795943-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006251.6(PRKAA1):​c.127+2120T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.16 in 152,248 control chromosomes in the GnomAD database, including 2,041 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 (2041 hom., cov: 32)
• Consequence: PRKAA1 NM_006251.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.69
• Publications: 15 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.24 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKAA1	NM_006251.6	c.127+2120T>C		intron_variant	Intron 1 of 8	ENST00000397128.7	NP_006242.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKAA1	ENST00000397128.7	c.127+2120T>C		intron_variant	Intron 1 of 8	1	NM_006251.6	ENSP00000380317.2

Frequencies

GnomAD3 genomes AF: 0.160 AC: 24372 AN: 152130 Hom.: 2038 Cov.: 32

Gnomad AFR AF: 0.195

Gnomad AMI AF: 0.154

Gnomad AMR AF: 0.152

Gnomad ASJ AF: 0.167

Gnomad EAS AF: 0.251

Gnomad SAS AF: 0.134

Gnomad FIN AF: 0.128

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.141

Gnomad OTH AF: 0.174

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

GnomAD4 genome AF: 0.160 AC: 24391 AN: 152248 Hom.: 2041 Cov.: 32 AF XY: 0.159 AC XY: 11819 AN XY: 74436

African (AFR) AF: 0.195 AC: 8086 AN: 41536

American (AMR) AF: 0.151 AC: 2316 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.167 AC: 580 AN: 3472

East Asian (EAS) AF: 0.251 AC: 1301 AN: 5182

South Asian (SAS) AF: 0.136 AC: 658 AN: 4832

European-Finnish (FIN) AF: 0.128 AC: 1352 AN: 10600

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.141 AC: 9561 AN: 68008

Other (OTH) AF: 0.171 AC: 362 AN: 2114

Alfa AF: 0.147 Hom.: 4758

Bravo AF: 0.165

Asia WGS AF: 0.184 AC: 641 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	9.3
DANN	Benign	0.66
PhyloP100		1.7
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: rs3805486; hg19: chr5-40796045;