NM_002862.4:c.280C>G

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_002862.4(PYGB):​c.280C>G​(p.Arg94Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,458,976 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 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. R94C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)
Exomes š‘“: 0.0000014 ( 0 hom. )

Consequence

PYGB
NM_002862.4 missense

Scores

15
3
1

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.76
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.974

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PYGBNM_002862.4 linkc.280C>G p.Arg94Gly missense_variant Exon 2 of 20 ENST00000216962.9 NP_002853.2 P11216
PYGBXM_047440342.1 linkc.280C>G p.Arg94Gly missense_variant Exon 2 of 16 XP_047296298.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PYGBENST00000216962.9 linkc.280C>G p.Arg94Gly missense_variant Exon 2 of 20 1 NM_002862.4 ENSP00000216962.3 P11216

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251404
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135878
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000879
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1458976
Hom.:
0
Cov.:
30
AF XY:
0.00000275
AC XY:
2
AN XY:
726002
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000180
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
ExAC
AF:
0.00000824
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.98
BayesDel_addAF
Pathogenic
0.50
D
BayesDel_noAF
Pathogenic
0.48
CADD
Pathogenic
31
DANN
Uncertain
1.0
DEOGEN2
Pathogenic
0.80
D
Eigen
Pathogenic
0.84
Eigen_PC
Pathogenic
0.72
FATHMM_MKL
Uncertain
0.84
D
LIST_S2
Pathogenic
0.99
D
M_CAP
Uncertain
0.24
D
MetaRNN
Pathogenic
0.97
D
MetaSVM
Pathogenic
1.1
D
MutationAssessor
Pathogenic
4.8
H
PrimateAI
Pathogenic
0.82
D
PROVEAN
Pathogenic
-5.7
D
REVEL
Pathogenic
0.93
Sift
Pathogenic
0.0
D
Sift4G
Pathogenic
0.0010
D
Polyphen
1.0
D
Vest4
0.98
MutPred
0.83
Loss of methylation at R94 (P = 0.0591);
MVP
0.98
MPC
0.90
ClinPred
1.0
D
GERP RS
4.4
Varity_R
0.92
gMVP
0.84

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs200651502; hg19: chr20-25239909; API