NM_005399.5:c.*1228G>A

Variant names:

• chr1-147158337-C-T
• rs10900321
• NM_005399.5:c.*1228G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005399.5(PRKAB2):​c.*1228G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.476 in 151,886 control chromosomes in the GnomAD database, including 18,336 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 0.48 (18336 hom., cov: 31)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: PRKAB2 NM_005399.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.82
• Publications: 16 publications found

Genes affected

PRKAB2 (HGNC:9379): (protein kinase AMP-activated non-catalytic subunit beta 2) 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. It is highly expressed in skeletal muscle and thus may have tissue-specific roles. Multiple alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jul 2013]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.837 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005399.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKAB2	NM_005399.5	MANE Select	c.*1228G>A		3_prime_UTR	Exon 8 of 8	NP_005390.1
	PRKAB2	NR_103870.2		n.1824G>A		non_coding_transcript_exon	Exon 6 of 6
	PRKAB2	NR_103871.2		n.1945G>A		non_coding_transcript_exon	Exon 7 of 7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKAB2	ENST00000254101.4	TSL:1 MANE Select	c.*1228G>A		3_prime_UTR	Exon 8 of 8	ENSP00000254101.3
	PRKAB2	ENST00000896001.1		c.*1228G>A		3_prime_UTR	Exon 7 of 7	ENSP00000566060.1
	PRKAB2	ENST00000896002.1		c.*1228G>A		3_prime_UTR	Exon 8 of 8	ENSP00000566061.1

Frequencies

GnomAD3 genomes AF: 0.476 AC: 72174 AN: 151764 Hom.: 18307 Cov.: 31

Gnomad AFR AF: 0.578

Gnomad AMI AF: 0.388

Gnomad AMR AF: 0.530

Gnomad ASJ AF: 0.360

Gnomad EAS AF: 0.858

Gnomad SAS AF: 0.558

Gnomad FIN AF: 0.479

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.373

Gnomad OTH AF: 0.457

GnomAD4 exome AF: 0.500 AC: 1 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AF: 0.500 AC: 1 AN: 2

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.476 AC: 72259 AN: 151884 Hom.: 18336 Cov.: 31 AF XY: 0.485 AC XY: 36014 AN XY: 74232

African (AFR) AF: 0.578 AC: 23952 AN: 41408

American (AMR) AF: 0.531 AC: 8095 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.360 AC: 1248 AN: 3462

East Asian (EAS) AF: 0.858 AC: 4431 AN: 5166

South Asian (SAS) AF: 0.557 AC: 2682 AN: 4814

European-Finnish (FIN) AF: 0.479 AC: 5041 AN: 10522

Middle Eastern (MID) AF: 0.527 AC: 155 AN: 294

European-Non Finnish (NFE) AF: 0.373 AC: 25327 AN: 67942

Other (OTH) AF: 0.462 AC: 974 AN: 2108

Alfa AF: 0.415 Hom.: 29596

Bravo AF: 0.483

Asia WGS AF: 0.678 AC: 2358 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	9.0
DANN	Benign	0.74
PhyloP100		1.8
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10900321; hg19: chr1-146629916;