rs372147025

Variant names:

• chr20-25296374-C-G
• rs372147025
• NM_002862.4:c.2384C>G

Your query was ambiguous. Multiple possible variants found:

• chr20-25296374-C-G
• chr20-25296374-C-T

Variant summary

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

The NM_002862.4(PYGB):​c.2384C>G​(p.Pro795Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: PYGB NM_002862.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.82

Genes affected

PYGB (HGNC:9723): (glycogen phosphorylase B) The protein encoded by this gene is a glycogen phosphorylase found predominantly in the brain. The encoded protein forms homodimers which can associate into homotetramers, the enzymatically active form of glycogen phosphorylase. The activity of this enzyme is positively regulated by AMP and negatively regulated by ATP, ADP, and glucose-6-phosphate. This enzyme catalyzes the rate-determining step in glycogen degradation. [provided by RefSeq, Jul 2008]

ABHD12 (HGNC:15868): (abhydrolase domain containing 12, lysophospholipase) This gene encodes an enzyme that catalyzes the hydrolysis of 2-arachidonoyl glycerol (2-AG), the main endocannabinoid lipid transmitter that acts on cannabinoid receptors, CB1 and CB2. The endocannabinoid system is involved in a wide range of physiological processes, including neurotransmission, mood, appetite, pain appreciation, addiction behavior, and inflammation. Mutations in this gene are associated with the neurodegenerative disease, PHARC (polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and cataract), resulting from an inborn error of endocannabinoid metabolism. Alternatively spliced transcript variants encoding different isoforms have been noted for this gene.[provided by RefSeq, Jan 2011]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PYGB	NM_002862.4	c.2384C>G	p.Pro795Arg	missense_variant	Exon 20 of 20	ENST00000216962.9	NP_002853.2
ABHD12	NM_015600.5	c.1158-1344G>C		intron_variant	Intron 12 of 12		NP_056415.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PYGB	ENST00000216962.9	c.2384C>G	p.Pro795Arg	missense_variant	Exon 20 of 20	1	NM_002862.4	ENSP00000216962.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.080
CADD	Uncertain	25
DANN	Benign	0.97
DEOGEN2	Uncertain	0.55	D
Eigen	Benign	-0.096
Eigen_PC	Benign	0.11
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.036	D
MetaRNN	Uncertain	0.50	D
MetaSVM	Uncertain	-0.14	T
MutationAssessor	Benign	1.4	L
PrimateAI	Benign	0.45	T
PROVEAN	Uncertain	-3.0	D
REVEL	Uncertain	0.58
Sift	Benign	0.25	T
Sift4G	Benign	0.57	T
Polyphen		0.011	B
Vest4		0.56
MutPred		0.49		Gain of MoRF binding (P = 0.0175);
MVP		0.93
MPC		0.25
ClinPred		0.91	D
GERP RS		4.8
Varity_R		0.59
gMVP		0.74

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

LitVar

Other links and lift over

dbSNP: rs372147025; hg19: chr20-25277010;