Variant rs650898 details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000439262.7(PRKAG3):c.73+45C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.917 in 1,455,936 control chromosomes in the GnomAD database, including 612,819 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 0.93 ( 66361 hom., cov: 30)

Exomes 𝑓: 0.92 ( 546458 hom. )

Consequence

PRKAG3
ENST00000439262.7 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.574

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 -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 = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRKAG3	NM_017431.4 linkuse as main transcript	c.73+45C>T		intron_variant		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.73+45C>T		intron_variant		1	NM_017431.4	ENSP00000397133	P1	Q9UGI9-1

Frequencies

GnomAD3 genomes

AF:

0.933

AC:

141878

AN:

152082

Hom.:

66304

Cov.:

show subpopulations

Gnomad AFR

AF:

0.985

Gnomad AMI

AF:

0.959

Gnomad AMR

AF:

0.930

Gnomad ASJ

AF:

0.920

Gnomad EAS

AF:

0.998

Gnomad SAS

AF:

0.906

Gnomad FIN

AF:

0.893

Gnomad MID

AF:

0.911

Gnomad NFE

AF:

0.906

Gnomad OTH

AF:

0.926

GnomAD3 exomes

AF:

0.922

AC:

165775

AN:

179836

Hom.:

76555

AF XY:

0.919

AC XY:

87614

AN XY:

95362

show subpopulations

Gnomad AFR exome

AF:

0.987

Gnomad AMR exome

AF:

0.925

Gnomad ASJ exome

AF:

0.923

Gnomad EAS exome

AF:

0.999

Gnomad SAS exome

AF:

0.906

Gnomad FIN exome

AF:

0.890

Gnomad NFE exome

AF:

0.906

Gnomad OTH exome

AF:

0.924

GnomAD4 exome

AF:

0.915

AC:

1193124

AN:

1303736

Hom.:

546458

Cov.:

AF XY:

0.915

AC XY:

589396

AN XY:

644384

show subpopulations

Gnomad4 AFR exome

AF:

0.988

Gnomad4 AMR exome

AF:

0.924

Gnomad4 ASJ exome

AF:

0.926

Gnomad4 EAS exome

AF:

0.999

Gnomad4 SAS exome

AF:

0.903

Gnomad4 FIN exome

AF:

0.890

Gnomad4 NFE exome

AF:

0.911

Gnomad4 OTH exome

AF:

0.919

GnomAD4 genome

AF:

0.933

AC:

141993

AN:

152200

Hom.:

66361

Cov.:

AF XY:

0.932

AC XY:

69376

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.985

Gnomad4 AMR

AF:

0.930

Gnomad4 ASJ

AF:

0.920

Gnomad4 EAS

AF:

0.998

Gnomad4 SAS

AF:

0.906

Gnomad4 FIN

AF:

0.893

Gnomad4 NFE

AF:

0.906

Gnomad4 OTH

AF:

0.927

Alfa

AF:

0.908

Hom.:

16462

Bravo

AF:

0.940

Asia WGS

AF:

0.964

AC:

3349

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

3.6

DANN

Benign

0.81

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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