chr5-40798137-T-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_006251.6(PRKAA1):ā€‹c.53A>Cā€‹(p.His18Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000136 in 1,605,056 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000046 ( 0 hom., cov: 30)
Exomes š‘“: 0.00015 ( 0 hom. )

Consequence

PRKAA1
NM_006251.6 missense

Scores

2
6
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.65
Variant links:
Genes affected
PRKAA1 (HGNC:9376): (protein kinase AMP-activated catalytic subunit alpha 1) The protein encoded by this gene belongs to the ser/thr protein kinase family. It is the catalytic subunit of the 5'-prime-AMP-activated protein kinase (AMPK). AMPK is a cellular energy sensor conserved in all eukaryotic cells. The kinase activity of AMPK is activated by the stimuli that increase the cellular AMP/ATP ratio. AMPK regulates the activities of a number of key metabolic enzymes through phosphorylation. It protects cells from stresses that cause ATP depletion by switching off ATP-consuming biosynthetic pathways. Alternatively spliced transcript variants encoding distinct isoforms have been observed. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2
High AC in GnomAd4 at 7 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PRKAA1NM_006251.6 linkuse as main transcriptc.53A>C p.His18Pro missense_variant 1/9 ENST00000397128.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PRKAA1ENST00000397128.7 linkuse as main transcriptc.53A>C p.His18Pro missense_variant 1/91 NM_006251.6 P1Q13131-1

Frequencies

GnomAD3 genomes
AF:
0.0000461
AC:
7
AN:
151708
Hom.:
0
Cov.:
30
show subpopulations
Gnomad AFR
AF:
0.0000484
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000737
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000449
AC:
11
AN:
245206
Hom.:
0
AF XY:
0.0000525
AC XY:
7
AN XY:
133254
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000993
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000146
AC:
212
AN:
1453348
Hom.:
0
Cov.:
32
AF XY:
0.000140
AC XY:
101
AN XY:
723234
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000186
Gnomad4 OTH exome
AF:
0.000100
GnomAD4 genome
AF:
0.0000461
AC:
7
AN:
151708
Hom.:
0
Cov.:
30
AF XY:
0.0000405
AC XY:
3
AN XY:
74086
show subpopulations
Gnomad4 AFR
AF:
0.0000484
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000737
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000193
Hom.:
0
Bravo
AF:
0.0000642
ExAC
AF:
0.0000247
AC:
3

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJan 26, 2022The c.53A>C (p.H18P) alteration is located in exon 1 (coding exon 1) of the PRKAA1 gene. This alteration results from a A to C substitution at nucleotide position 53, causing the histidine (H) at amino acid position 18 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.089
BayesDel_addAF
Benign
0.00082
T
BayesDel_noAF
Uncertain
-0.030
CADD
Uncertain
24
DANN
Benign
0.94
DEOGEN2
Benign
0.068
T;.;T
Eigen
Uncertain
0.23
Eigen_PC
Uncertain
0.27
FATHMM_MKL
Benign
0.71
D
LIST_S2
Uncertain
0.88
D;D;D
M_CAP
Pathogenic
0.83
D
MetaRNN
Uncertain
0.62
D;D;D
MetaSVM
Benign
-0.63
T
MutationAssessor
Benign
-0.27
N;N;.
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Pathogenic
0.93
D
PROVEAN
Benign
0.72
N;N;N
REVEL
Uncertain
0.40
Sift
Benign
0.24
T;T;T
Sift4G
Benign
0.29
T;T;T
Polyphen
0.92
P;P;.
Vest4
0.64
MVP
0.78
MPC
1.7
ClinPred
0.31
T
GERP RS
4.1
Varity_R
0.26
gMVP
0.49

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: rs749919427; hg19: chr5-40798239; API