Genetic Variant PRKAB1:c.-120C>T (chr12-119667935-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000541640.5(PRKAB1):c.-120C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000948 in 211,024 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 34)

Exomes 𝑓: 0.0000095 ( 0 hom. )

Consequence

PRKAB1
ENST00000541640.5 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.33

Publications

0 publications found

Variant links:

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 links:

ENSG00000248636 (HGNC:58183):

ENSG00000248636 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000541640.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank
PRKAB1-AS1	NR_188490.1	n.185+8G>A	splice_region intron	N/A
PRKAB1-AS1	NR_188492.1	n.185+8G>A	splice_region intron	N/A
PRKAB1-AS1	NR_188494.1	n.185+8G>A	splice_region intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
PRKAB1	ENST00000541640.5	TSL:1	c.-120C>T	5_prime_UTR_premature_start_codon_gain	Exon 1 of 8	ENSP00000441369.1
PRKAB1	ENST00000541640.5	TSL:1	c.-120C>T	5_prime_UTR	Exon 1 of 8	ENSP00000441369.1
ENSG00000248636	ENST00000537366.6	TSL:3	n.153+8G>A	splice_region intron	N/A

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000948

AC:

AN:

211024

Hom.:

Cov.:

AF XY:

0.0000183

AC XY:

AN XY:

109006

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

4870

American (AMR)

AF:

0.00

AC:

AN:

4034

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

7558

East Asian (EAS)

AF:

0.00

AC:

AN:

11604

South Asian (SAS)

AF:

0.0000483

AC:

AN:

20706

European-Finnish (FIN)

AF:

0.00

AC:

AN:

15008

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1090

European-Non Finnish (NFE)

AF:

0.00000755

AC:

AN:

132518

Other (OTH)

AF:

0.00

AC:

AN:

13636

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.61

(source)

DANN

Benign

0.87

PhyloP100

-2.3

PromoterAI

-0.037

Neutral

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over