ENST00000691528.3:n.302C>T

Variant names:

• chr5-40798542-C-T
• rs10035235
• ENST00000691528.3:n.302C>T

Variant summary

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

The ENST00000691528.3(ENSG00000288911):​n.302C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.219 in 152,192 control chromosomes in the GnomAD database, including 4,416 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 0.22 (4416 hom., cov: 32)
• Consequence: ENSG00000288911 ENST00000691528.3 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.95
• Publications: 6 publications found

Genes affected

ENSG00000288911 (HGNC:59033):

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=-0.81).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.37 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000691528.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKAA1	NM_006251.6	MANE Select	c.-353G>A		upstream_gene	N/A	NP_006242.5
	PRKAA1	NM_206907.4		c.-353G>A		upstream_gene	N/A	NP_996790.3
	PRKAA1	NM_001355034.2		c.-353G>A		upstream_gene	N/A	NP_001341963.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000288911	ENST00000691528.3		n.302C>T		non_coding_transcript_exon	Exon 1 of 1
	PRKAA1	ENST00000397128.7	TSL:1 MANE Select	c.-353G>A		upstream_gene	N/A	ENSP00000380317.2	Q13131-1
	PRKAA1	ENST00000354209.7	TSL:1	c.-353G>A		upstream_gene	N/A	ENSP00000346148.3	Q13131-2

Frequencies

GnomAD3 genomes AF: 0.219 AC: 33325 AN: 152074 Hom.: 4407 Cov.: 32

Gnomad AFR AF: 0.0950

Gnomad AMI AF: 0.182

Gnomad AMR AF: 0.378

Gnomad ASJ AF: 0.216

Gnomad EAS AF: 0.215

Gnomad SAS AF: 0.331

Gnomad FIN AF: 0.185

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.257

Gnomad OTH AF: 0.233

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

GnomAD4 genome AF: 0.219 AC: 33341 AN: 152192 Hom.: 4416 Cov.: 32 AF XY: 0.222 AC XY: 16521 AN XY: 74404

African (AFR) AF: 0.0949 AC: 3942 AN: 41556

American (AMR) AF: 0.378 AC: 5785 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.216 AC: 748 AN: 3470

East Asian (EAS) AF: 0.214 AC: 1105 AN: 5158

South Asian (SAS) AF: 0.331 AC: 1598 AN: 4826

European-Finnish (FIN) AF: 0.185 AC: 1956 AN: 10592

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.257 AC: 17488 AN: 67980

Other (OTH) AF: 0.230 AC: 487 AN: 2114

Alfa AF: 0.254 Hom.: 6724

Bravo AF: 0.228

Asia WGS AF: 0.279 AC: 973 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.55
DANN	Benign	0.95
PhyloP100		-2.0
PromoterAI		0.046	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs10035235;

hg19: chr5-40798644;