12-119681378-T-G

Position:

• chr12-119681378-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006253.5(PRKAB1):​c.*1053T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.325 in 152,076 control chromosomes in the GnomAD database, including 8,624 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 0.33 (8620 hom., cov: 32)
  • Exomes 𝑓: 0.26 (4 hom.)
• Consequence: PRKAB1 NM_006253.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.841

Genes affected

PRKAB1 (HGNC:9378): (protein kinase AMP-activated non-catalytic subunit beta 1) 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 may be a positive regulator of AMPK activity. The myristoylation and phosphorylation of this subunit have been shown to affect the enzyme activity and cellular localization of AMPK. This subunit may also serve as an adaptor molecule mediating the association of the AMPK complex. [provided by RefSeq, Jul 2008]

PRKAB1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.419 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRKAB1	NM_006253.5	c.*1053T>G		3_prime_UTR_variant	7/7	ENST00000229328.10	NP_006244.2
PRKAB1	XM_005253909.2	c.*1053T>G		3_prime_UTR_variant	8/8		XP_005253966.1
LOC124903033	XR_007063485.1	n.165+3944A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRKAB1	ENST00000229328.10	c.*1053T>G		3_prime_UTR_variant	7/7	1	NM_006253.5	ENSP00000229328.5
PRKAB1	ENST00000541640.5	c.*1053T>G		3_prime_UTR_variant	8/8	1		ENSP00000441369.1
PRKAB1	ENST00000542698.1	n.3778T>G		non_coding_transcript_exon_variant	2/2	1
PRKAB1	ENST00000537057.1	n.1301T>G		non_coding_transcript_exon_variant	1/1	6

Frequencies

GnomAD3 genomes AF: 0.325 AC: 49395 AN: 151852 Hom.: 8613 Cov.: 32

Gnomad AFR AF: 0.424

Gnomad AMI AF: 0.159

Gnomad AMR AF: 0.256

Gnomad ASJ AF: 0.284

Gnomad EAS AF: 0.0139

Gnomad SAS AF: 0.206

Gnomad FIN AF: 0.277

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.325

Gnomad OTH AF: 0.315

GnomAD4 exome AF: 0.259 AC: 28 AN: 108 Hom.: 4 Cov.: 0 AF XY: 0.241 AC XY: 13 AN XY: 54

Gnomad4 FIN exome AF: 0.293

Gnomad4 NFE exome AF: 0.100

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.325 AC: 49421 AN: 151968 Hom.: 8620 Cov.: 32 AF XY: 0.318 AC XY: 23586 AN XY: 74284

Gnomad4 AFR AF: 0.424

Gnomad4 AMR AF: 0.256

Gnomad4 ASJ AF: 0.284

Gnomad4 EAS AF: 0.0139

Gnomad4 SAS AF: 0.206

Gnomad4 FIN AF: 0.277

Gnomad4 NFE AF: 0.325

Gnomad4 OTH AF: 0.311

Alfa AF: 0.334 Hom.: 1565

Bravo AF: 0.326

Asia WGS AF: 0.136 AC: 477 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.14
DANN	Benign	0.46
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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

Other links and lift over

dbSNP: rs4213; hg19: chr12-120119183;