rs144426409

Variant names:

• chr7-151876510-A-C
• NM_016203.4:c.111T>G

Your query was ambiguous. Multiple possible variants found:

• chr7-151876510-A-C
• chr7-151876510-A-G
• chr7-151876510-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_016203.4(PRKAG2):​c.111T>G​(p.Ile37Met) 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. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. I37I) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PRKAG2 NM_016203.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.350

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11734402).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKAG2	NM_016203.4	c.111T>G	p.Ile37Met	missense_variant	Exon 1 of 16	ENST00000287878.9	NP_057287.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKAG2	ENST00000287878.9	c.111T>G	p.Ile37Met	missense_variant	Exon 1 of 16	1	NM_016203.4	ENSP00000287878.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Hypertrophic cardiomyopathy Uncertain:1

Apr 27, 2023

All of Us Research Program, National Institutes of Health

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
CardioboostCm	Uncertain	0.17
BayesDel_addAF	Uncertain	0.042	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	14
DANN	Benign	0.73
DEOGEN2	Benign	0.050	T
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.18
FATHMM_MKL	Benign	0.39	N
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.055	D
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.35	T
MutationAssessor	Benign	0.41	N
PrimateAI	Pathogenic	0.80	D
PROVEAN	Benign	0.16	N
REVEL	Uncertain	0.38
Sift	Benign	0.41	T
Sift4G	Benign	0.51	T
Polyphen		0.033	B
Vest4		0.39
MutPred		0.33		Loss of sheet (P = 0.0457);
MVP		0.78
MPC		1.1
ClinPred		0.41	T
GERP RS		1.6
Varity_R		0.16
gMVP		0.17

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-151573595;