Variant chr2-218830071-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP7BS1BS2

The NM_017431.4(PRKAG3):c.540C>T(p.Gly180=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0278 in 1,613,550 control chromosomes in the GnomAD database, including 725 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 0.020 ( 49 hom., cov: 32)

Exomes 𝑓: 0.029 ( 676 hom. )

Consequence

PRKAG3
NM_017431.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.792

Variant links:

Genes affected

PRKAG3 (HGNC:9387): (protein kinase AMP-activated non-catalytic subunit gamma 3) 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. It is dominantly expressed in skeletal muscle. Studies of the pig counterpart suggest that this subunit may play a key role in the regulation of energy metabolism in skeletal muscle. [provided by RefSeq, Jul 2008]

PRKAG3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.42).

BP7

Synonymous conserved (PhyloP=-0.792 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0205 (3122/152310) while in subpopulation NFE AF= 0.031 (2111/68032). AF 95% confidence interval is 0.0299. There are 49 homozygotes in gnomad4. There are 1434 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 3122 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRKAG3	NM_017431.4 linkuse as main transcript	c.540C>T	p.Gly180=	synonymous_variant	4/14	ENST00000439262.7	NP_059127.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRKAG3	ENST00000439262.7 linkuse as main transcript	c.540C>T	p.Gly180=	synonymous_variant	4/14	1	NM_017431.4	ENSP00000397133	P1	Q9UGI9-1
PRKAG3	ENST00000529249.5 linkuse as main transcript	c.540C>T	p.Gly180=	synonymous_variant	4/13	1		ENSP00000436068	P1	Q9UGI9-1
PRKAG3	ENST00000490971.1 linkuse as main transcript	n.573C>T		non_coding_transcript_exon_variant	4/9	2
PRKAG3	ENST00000470307.6 linkuse as main transcript	c.540C>T	p.Gly180=	synonymous_variant, NMD_transcript_variant	4/11	5		ENSP00000419272

Frequencies

GnomAD3 genomes

AF:

0.0205

AC:

3122

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00601

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.0151

Gnomad ASJ

AF:

0.0282

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00476

Gnomad FIN

AF:

0.0338

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0310

Gnomad OTH

AF:

0.0220

GnomAD3 exomes

AF:

0.0216

AC:

5416

AN:

250866

Hom.:

AF XY:

0.0217

AC XY:

2942

AN XY:

135526

show subpopulations

Gnomad AFR exome

AF:

0.00542

Gnomad AMR exome

AF:

0.0127

Gnomad ASJ exome

AF:

0.0271

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00603

Gnomad FIN exome

AF:

0.0353

Gnomad NFE exome

AF:

0.0311

Gnomad OTH exome

AF:

0.0235

GnomAD4 exome

AF:

0.0286

AC:

41800

AN:

1461240

Hom.:

676

Cov.:

AF XY:

0.0279

AC XY:

20285

AN XY:

726808

show subpopulations

Gnomad4 AFR exome

AF:

0.00370

Gnomad4 AMR exome

AF:

0.0135

Gnomad4 ASJ exome

AF:

0.0270

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00659

Gnomad4 FIN exome

AF:

0.0359

Gnomad4 NFE exome

AF:

0.0327

Gnomad4 OTH exome

AF:

0.0246

GnomAD4 genome

AF:

0.0205

AC:

3122

AN:

152310

Hom.:

Cov.:

AF XY:

0.0193

AC XY:

1434

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.00599

Gnomad4 AMR

AF:

0.0151

Gnomad4 ASJ

AF:

0.0282

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00477

Gnomad4 FIN

AF:

0.0338

Gnomad4 NFE

AF:

0.0310

Gnomad4 OTH

AF:

0.0218

Alfa

AF:

0.0229

Hom.:

Bravo

AF:

0.0189

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.0296

EpiControl

AF:

0.0335

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.42

CADD

Benign

7.3

DANN

Benign

0.88

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