Variant 1-56674374-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_006252.4(PRKAA2):c.95-7T>C variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0106 in 1,529,408 control chromosomes in the GnomAD database, including 96 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0076 ( 6 hom., cov: 33)

Exomes 𝑓: 0.011 ( 90 hom. )

Consequence

PRKAA2
NM_006252.4 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00001373

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.126

Variant links:

Genes affected

PRKAA2 (HGNC:9377): (protein kinase AMP-activated catalytic subunit alpha 2) The protein encoded by this gene is a catalytic 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. Studies of the mouse counterpart suggest that this catalytic subunit may control whole-body insulin sensitivity and is necessary for maintaining myocardial energy homeostasis during ischemia. [provided by RefSeq, Jul 2008]

PRKAA2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 1-56674374-T-C is Benign according to our data. Variant chr1-56674374-T-C is described in ClinVar as [Benign]. Clinvar id is 774155.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd at 1163 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRKAA2	NM_006252.4 linkuse as main transcript	c.95-7T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000371244.9
PRKAA2	XM_017001693.2 linkuse as main transcript	c.-176-7T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKAA2	ENST00000371244.9 linkuse as main transcript	c.95-7T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_006252.4	P1

Frequencies

GnomAD3 genomes

AF:

0.00765

AC:

1163

AN:

152014

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00193

Gnomad AMI

AF:

0.00658

Gnomad AMR

AF:

0.00308

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00228

Gnomad FIN

AF:

0.0161

Gnomad MID

AF:

0.00955

Gnomad NFE

AF:

0.0124

Gnomad OTH

AF:

0.00240

GnomAD3 exomes

AF:

0.00814

AC:

1539

AN:

188996

Hom.:

AF XY:

0.00824

AC XY:

860

AN XY:

104352

show subpopulations

Gnomad AFR exome

AF:

0.00178

Gnomad AMR exome

AF:

0.00287

Gnomad ASJ exome

AF:

0.000288

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00464

Gnomad FIN exome

AF:

0.0168

Gnomad NFE exome

AF:

0.0107

Gnomad OTH exome

AF:

0.00623

GnomAD4 exome

AF:

0.0109

AC:

15064

AN:

1377276

Hom.:

Cov.:

AF XY:

0.0106

AC XY:

7239

AN XY:

683678

show subpopulations

Gnomad4 AFR exome

AF:

0.00142

Gnomad4 AMR exome

AF:

0.00329

Gnomad4 ASJ exome

AF:

0.000176

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00535

Gnomad4 FIN exome

AF:

0.0174

Gnomad4 NFE exome

AF:

0.0121

Gnomad4 OTH exome

AF:

0.0107

GnomAD4 genome

AF:

0.00764

AC:

1163

AN:

152132

Hom.:

Cov.:

AF XY:

0.00773

AC XY:

575

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.00192

Gnomad4 AMR

AF:

0.00308

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00228

Gnomad4 FIN

AF:

0.0161

Gnomad4 NFE

AF:

0.0124

Gnomad4 OTH

AF:

0.00238

Alfa

AF:

0.00956

Hom.:

Bravo

AF:

0.00615

Asia WGS

AF:

0.00116

AC:

AN:

3466

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 06, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

Cadd

Benign

1.9

Dann

Benign

0.58

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000014

dbscSNV1_RF

Benign

0.0

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over