Menu
GeneBe

1-56704121-T-C

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_006252.4(PRKAA2):c.939T>C(p.Ser313=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00427 in 1,614,184 control chromosomes in the GnomAD database, including 25 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0037 ( 4 hom., cov: 32)
Exomes 𝑓: 0.0043 ( 21 hom. )

Consequence

PRKAA2
NM_006252.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.216
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.51).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 1-56704121-T-C is Benign according to our data. Variant chr1-56704121-T-C is described in ClinVar as [Benign]. Clinvar id is 779398.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.216 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 566 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PRKAA2NM_006252.4 linkuse as main transcriptc.939T>C p.Ser313= synonymous_variant 7/9 ENST00000371244.9
PRKAA2XM_017001693.2 linkuse as main transcriptc.669T>C p.Ser223= synonymous_variant 7/9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PRKAA2ENST00000371244.9 linkuse as main transcriptc.939T>C p.Ser313= synonymous_variant 7/91 NM_006252.4 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00372
AC:
566
AN:
152192
Hom.:
4
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000989
Gnomad AMI
AF:
0.00110
Gnomad AMR
AF:
0.00236
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00914
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00566
Gnomad OTH
AF:
0.00239
GnomAD3 exomes
AF:
0.00330
AC:
830
AN:
251364
Hom.:
1
AF XY:
0.00295
AC XY:
401
AN XY:
135840
show subpopulations
Gnomad AFR exome
AF:
0.000738
Gnomad AMR exome
AF:
0.00260
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000359
Gnomad FIN exome
AF:
0.00864
Gnomad NFE exome
AF:
0.00443
Gnomad OTH exome
AF:
0.00424
GnomAD4 exome
AF:
0.00433
AC:
6333
AN:
1461874
Hom.:
21
Cov.:
31
AF XY:
0.00428
AC XY:
3114
AN XY:
727238
show subpopulations
Gnomad4 AFR exome
AF:
0.000538
Gnomad4 AMR exome
AF:
0.00239
Gnomad4 ASJ exome
AF:
0.0000765
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000371
Gnomad4 FIN exome
AF:
0.00874
Gnomad4 NFE exome
AF:
0.00488
Gnomad4 OTH exome
AF:
0.00459
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00372
AC:
566
AN:
152310
Hom.:
4
Cov.:
32
AF XY:
0.00349
AC XY:
260
AN XY:
74480
show subpopulations
Gnomad4 AFR
AF:
0.000986
Gnomad4 AMR
AF:
0.00235
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00914
Gnomad4 NFE
AF:
0.00566
Gnomad4 OTH
AF:
0.00237
Alfa
AF:
0.00470
Hom.:
0
Bravo
AF:
0.00307
EpiCase
AF:
0.00453
EpiControl
AF:
0.00344

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJul 20, 2018- -
PRKAA2-related disorder Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesJun 12, 2019This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.51
Cadd
Benign
6.1
Dann
Benign
0.73

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.

Other links and lift over

dbSNP: rs41285004; hg19: chr1-57169794; API