NM_016203.4:c.32A>T

Variant names:

• chr7-151876589-T-A
• rs1060503025
• NM_016203.4:c.32A>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_016203.4(PRKAG2):​c.32A>T​(p.Lys11Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K11E) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PRKAG2 NM_016203.4 missense
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:3
• Conservation: PhyloP100: 2.42
• Publications: 0 publications found

Genes affected

PRKAG2 (HGNC:9386): (protein kinase AMP-activated non-catalytic subunit gamma 2) AMP-activated protein kinase (AMPK) is a heterotrimeric protein composed of a catalytic alpha subunit, a noncatalytic beta subunit, and a noncatalytic regulatory gamma subunit. Various forms of each of these subunits exist, encoded by different genes. AMPK is an important energy-sensing enzyme that monitors cellular energy status and functions by inactivating key enzymes involved in regulating de novo biosynthesis of fatty acid and cholesterol. This gene is a member of the AMPK gamma subunit family. Mutations in this gene have been associated with Wolff-Parkinson-White syndrome, familial hypertrophic cardiomyopathy, and glycogen storage disease of the heart. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jan 2015]

PRKAG2-AS1 (HGNC:40468): (PRKAG2 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.33943892).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016203.4. 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
	PRKAG2	NM_016203.4	MANE Select	c.32A>T	p.Lys11Ile	missense	Exon 1 of 16	NP_057287.2
	PRKAG2	NM_001407021.1		c.32A>T	p.Lys11Ile	missense	Exon 1 of 15	NP_001393950.1
	PRKAG2	NM_001407022.1		c.32A>T	p.Lys11Ile	missense	Exon 1 of 15	NP_001393951.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKAG2	ENST00000287878.9	TSL:1 MANE Select	c.32A>T	p.Lys11Ile	missense	Exon 1 of 16	ENSP00000287878.3	Q9UGJ0-1
	PRKAG2	ENST00000488258.5	TSL:1	n.32A>T		non_coding_transcript_exon	Exon 1 of 10	ENSP00000420783.1	F8WDA1
	PRKAG2	ENST00000652321.2		c.32A>T	p.Lys11Ile	missense	Exon 1 of 16	ENSP00000498886.2	A0A494C155

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	1	-	Cardiovascular phenotype (1)
-	1	-	Lethal congenital glycogen storage disease of heart (1)
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.51
CardioboostCm	Uncertain	0.12
BayesDel_addAF	Uncertain	0.098	D
BayesDel_noAF	Benign	-0.10
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.14	T
Eigen	Uncertain	0.21
Eigen_PC	Benign	0.19
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.78	T
M_CAP	Uncertain	0.17	D
MetaRNN	Benign	0.34	T
MetaSVM	Uncertain	0.071	D
MutationAssessor	Benign	1.6	L
PhyloP100		2.4
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-1.1	N
REVEL	Uncertain	0.47
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.033	D
Polyphen		0.97	D
Vest4		0.40
MutPred		0.37		Loss of solvent accessibility (P = 0.0045)
MVP		0.78
MPC		2.1
ClinPred		0.92	D
GERP RS		2.8
Varity_R		0.42
gMVP		0.44
Mutation Taster		=75/25	polymorphism

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: rs1060503025; hg19: chr7-151573674;