12-49002905-C-A

Position:

• chr12-49002905-C-A

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP6

The ENST00000548065.7(PRKAG1):​c.990G>T​(p.Lys330Asn) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PRKAG1 ENST00000548065.7 missense
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.515

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]

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

ACMG classification

Verdict is Likely_benign. Variant got -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1836625).
• BP6: Variant 12-49002905-C-A is Benign according to our data. Variant chr12-49002905-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 2681501.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRKAG1	NM_002733.5	c.990G>T	p.Lys330Asn	missense_variant	12/12	ENST00000548065.7	NP_002724.1
DDN-AS1	NR_147178.1	n.344+4215C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRKAG1	ENST00000548065.7	c.990G>T	p.Lys330Asn	missense_variant	12/12	1	NM_002733.5	ENSP00000447433	P4
DDN-AS1	ENST00000552933.2	n.324+4215C>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

EBV-positive nodal T- and NK-cell lymphoma Benign:1

Likely benign, no assertion criteria provided

research

Department of Clinical Pathology, School of Medicine, Fujita Health University

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.054	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.067	.;.;T;.;.
Eigen	Benign	-0.47
Eigen_PC	Benign	-0.40
FATHMM_MKL	Benign	0.30	N
LIST_S2	Benign	0.81	T;T;T;T;T
M_CAP	Benign	0.050	D
MetaRNN	Benign	0.18	T;T;T;T;T
MetaSVM	Benign	-0.58	T
MutationAssessor	Benign	0.69	.;.;N;.;.
MutationTaster	Benign	0.69	D;N;N;N;N
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-0.13	N;N;N;N;N
REVEL	Benign	0.20
Sift	Benign	0.12	T;T;D;D;T
Sift4G	Benign	0.20	T;T;T;T;T
Polyphen		0.15	.;.;B;.;.
Vest4		0.098
MutPred		0.38		.;.;Loss of methylation at K330 (P = 8e-04);.;.;
MVP		0.94
MPC		0.72
ClinPred		0.26	T
GERP RS		0.67
Varity_R		0.046
gMVP		0.55

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: chr12-49396688;