Variant chr12-49005079-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002733.5(PRKAG1):c.355+41C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.381 in 1,612,624 control chromosomes in the GnomAD database, including 118,934 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 0.36 ( 10117 hom., cov: 31)

Exomes 𝑓: 0.38 ( 108817 hom. )

Consequence

PRKAG1
NM_002733.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.400

Variant links:

Genes affected

PRKAG1 (HGNC:9385): (protein kinase AMP-activated non-catalytic subunit gamma 1) The protein encoded by this gene is a regulatory subunit of the AMP-activated protein kinase (AMPK). AMPK is a heterotrimer consisting of an alpha catalytic subunit, and non-catalytic beta and gamma subunits. AMPK is an important energy-sensing enzyme that monitors cellular energy status. In response to cellular metabolic stresses, AMPK is activated, and thus phosphorylates and inactivates acetyl-CoA carboxylase (ACC) and beta-hydroxy beta-methylglutaryl-CoA reductase (HMGCR), key enzymes involved in regulating de novo biosynthesis of fatty acid and cholesterol. This subunit is one of the gamma regulatory subunits of AMPK. Alternatively spliced transcript variants encoding distinct isoforms have been observed. [provided by RefSeq, Jul 2008]

PRKAG1 links:

DDN-AS1 (HGNC:53464): (DDN and PRKAG1 antisense RNA 1)

DDN-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.434 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRKAG1	NM_002733.5 linkuse as main transcript	c.355+41C>T		intron_variant		ENST00000548065.7	NP_002724.1
DDN-AS1	NR_147178.1 linkuse as main transcript	n.345-4230G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRKAG1	ENST00000548065.7 linkuse as main transcript	c.355+41C>T		intron_variant		1	NM_002733.5	ENSP00000447433	P4	P54619-1
DDN-AS1	ENST00000552933.2 linkuse as main transcript	n.324+6389G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.362

AC:

54854

AN:

151680

Hom.:

10104

Cov.:

show subpopulations

Gnomad AFR

AF:

0.321

Gnomad AMI

AF:

0.355

Gnomad AMR

AF:

0.312

Gnomad ASJ

AF:

0.244

Gnomad EAS

AF:

0.425

Gnomad SAS

AF:

0.449

Gnomad FIN

AF:

0.413

Gnomad MID

AF:

0.253

Gnomad NFE

AF:

0.386

Gnomad OTH

AF:

0.336

GnomAD3 exomes

AF:

0.366

AC:

92097

AN:

251386

Hom.:

17445

AF XY:

0.373

AC XY:

50699

AN XY:

135888

show subpopulations

Gnomad AFR exome

AF:

0.321

Gnomad AMR exome

AF:

0.261

Gnomad ASJ exome

AF:

0.251

Gnomad EAS exome

AF:

0.436

Gnomad SAS exome

AF:

0.431

Gnomad FIN exome

AF:

0.413

Gnomad NFE exome

AF:

0.378

Gnomad OTH exome

AF:

0.362

GnomAD4 exome

AF:

0.383

AC:

559450

AN:

1460826

Hom.:

108817

Cov.:

AF XY:

0.384

AC XY:

279100

AN XY:

726842

show subpopulations

Gnomad4 AFR exome

AF:

0.318

Gnomad4 AMR exome

AF:

0.265

Gnomad4 ASJ exome

AF:

0.256

Gnomad4 EAS exome

AF:

0.397

Gnomad4 SAS exome

AF:

0.427

Gnomad4 FIN exome

AF:

0.413

Gnomad4 NFE exome

AF:

0.388

Gnomad4 OTH exome

AF:

0.378

GnomAD4 genome

AF:

0.362

AC:

54905

AN:

151798

Hom.:

10117

Cov.:

AF XY:

0.362

AC XY:

26815

AN XY:

74156

show subpopulations

Gnomad4 AFR

AF:

0.322

Gnomad4 AMR

AF:

0.311

Gnomad4 ASJ

AF:

0.244

Gnomad4 EAS

AF:

0.425

Gnomad4 SAS

AF:

0.450

Gnomad4 FIN

AF:

0.413

Gnomad4 NFE

AF:

0.386

Gnomad4 OTH

AF:

0.336

Alfa

AF:

0.371

Hom.:

13778

Bravo

AF:

0.346

Asia WGS

AF:

0.426

AC:

1481

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

3.5

DANN

Benign

0.54

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over