12-49003818-AT-GA

Variant names:

• chr12-49003818-AT-GA
• NM_002733.5:c.641_642delATinsTC
• PRKAG1 p.Tyr214Phe

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_002733.5(PRKAG1):​c.641_642delATinsTC​(p.Tyr214Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Y214C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: PRKAG1 NM_002733.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.60
• Publications: 0 publications found

Genes affected

PRKAG1 (HGNC:9385): (protein kinase AMP-activated non-catalytic subunit gamma 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 is one of the gamma regulatory subunits of AMPK. Alternatively spliced transcript variants encoding distinct isoforms have been observed. [provided by RefSeq, Jul 2008]

ENSG00000288710 (HGNC:):

DDN-AS1 (HGNC:53464): (DDN and PRKAG1 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002733.5. 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
	PRKAG1	NM_002733.5	MANE Select	c.641_642delATinsTC	p.Tyr214Phe	missense	N/A	NP_002724.1	P54619-1
	PRKAG1	NM_001206709.2		c.668_669delATinsTC	p.Tyr223Phe	missense	N/A	NP_001193638.1	P54619-3
	PRKAG1	NM_001206710.2		c.545_546delATinsTC	p.Tyr182Phe	missense	N/A	NP_001193639.1	P54619-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKAG1	ENST00000548065.7	TSL:1 MANE Select	c.641_642delATinsTC	p.Tyr214Phe	missense	N/A	ENSP00000447433.1	P54619-1
	ENSG00000288710	ENST00000683988.1		n.*708_*709delATinsTC		non_coding_transcript_exon	Exon 13 of 16	ENSP00000506939.1	A0A804HI77
	ENSG00000288710	ENST00000683988.1		n.*708_*709delATinsTC		3_prime_UTR	Exon 13 of 16	ENSP00000506939.1	A0A804HI77

Frequencies

GnomAD3 genomes Cov.: 31

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.6

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr12-49397601;