chr5-40765115-T-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_006251.6(PRKAA1):ā€‹c.945A>Gā€‹(p.Glu315=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00266 in 1,614,196 control chromosomes in the GnomAD database, including 60 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā˜…ā˜…).

Frequency

Genomes: š‘“ 0.0021 ( 4 hom., cov: 32)
Exomes š‘“: 0.0027 ( 56 hom. )

Consequence

PRKAA1
NM_006251.6 synonymous

Scores

2

Clinical Significance

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

Conservation

PhyloP100: 0.234
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 Benign. Variant got -21 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.55).
BP6
Variant 5-40765115-T-C is Benign according to our data. Variant chr5-40765115-T-C is described in ClinVar as [Benign]. Clinvar id is 725539.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=0.234 with no splicing effect.
BS1
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00214 (326/152332) while in subpopulation SAS AF= 0.0184 (89/4828). AF 95% confidence interval is 0.0153. There are 4 homozygotes in gnomad4. There are 193 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High AC in GnomAd4 at 326 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PRKAA1NM_006251.6 linkuse as main transcriptc.945A>G p.Glu315= synonymous_variant 7/9 ENST00000397128.7 NP_006242.5
LOC124900968XR_007058747.1 linkuse as main transcriptn.1451+648T>C intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PRKAA1ENST00000397128.7 linkuse as main transcriptc.945A>G p.Glu315= synonymous_variant 7/91 NM_006251.6 ENSP00000380317 P1Q13131-1
PRKAA1ENST00000354209.7 linkuse as main transcriptc.990A>G p.Glu330= synonymous_variant 8/101 ENSP00000346148 Q13131-2
PRKAA1ENST00000505783.5 linkuse as main transcriptn.574A>G non_coding_transcript_exon_variant 4/42
PRKAA1ENST00000506652.5 linkuse as main transcriptn.904A>G non_coding_transcript_exon_variant 7/75

Frequencies

GnomAD3 genomes
AF:
0.00215
AC:
328
AN:
152214
Hom.:
4
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00530
Gnomad ASJ
AF:
0.00691
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.0180
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.0382
Gnomad NFE
AF:
0.00144
Gnomad OTH
AF:
0.00766
GnomAD3 exomes
AF:
0.00440
AC:
1098
AN:
249534
Hom.:
15
AF XY:
0.00544
AC XY:
736
AN XY:
135374
show subpopulations
Gnomad AFR exome
AF:
0.000323
Gnomad AMR exome
AF:
0.00226
Gnomad ASJ exome
AF:
0.00913
Gnomad EAS exome
AF:
0.0000556
Gnomad SAS exome
AF:
0.0210
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00208
Gnomad OTH exome
AF:
0.00726
GnomAD4 exome
AF:
0.00272
AC:
3973
AN:
1461864
Hom.:
56
Cov.:
31
AF XY:
0.00335
AC XY:
2433
AN XY:
727236
show subpopulations
Gnomad4 AFR exome
AF:
0.000597
Gnomad4 AMR exome
AF:
0.00239
Gnomad4 ASJ exome
AF:
0.00804
Gnomad4 EAS exome
AF:
0.0000756
Gnomad4 SAS exome
AF:
0.0199
Gnomad4 FIN exome
AF:
0.000131
Gnomad4 NFE exome
AF:
0.00130
Gnomad4 OTH exome
AF:
0.00407
GnomAD4 genome
AF:
0.00214
AC:
326
AN:
152332
Hom.:
4
Cov.:
32
AF XY:
0.00259
AC XY:
193
AN XY:
74494
show subpopulations
Gnomad4 AFR
AF:
0.000241
Gnomad4 AMR
AF:
0.00529
Gnomad4 ASJ
AF:
0.00691
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.0184
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00144
Gnomad4 OTH
AF:
0.00710
Alfa
AF:
0.00231
Hom.:
1
Bravo
AF:
0.00177
Asia WGS
AF:
0.00635
AC:
22
AN:
3478
EpiCase
AF:
0.00365
EpiControl
AF:
0.00290

ClinVar

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

Submissions by phenotype

not provided Benign:2
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJul 31, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.55
CADD
Benign
7.0
DANN
Benign
0.46
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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: rs56138995; hg19: chr5-40765217; API