Genetic Variant NM_002862.4:c.88A>C (chr20-25248266-A-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_002862.4(PYGB):c.88A>C(p.Lys30Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000522 in 1,600,874 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00030 ( 0 hom., cov: 34)

Exomes 𝑓: 0.00055 ( 0 hom. )

Consequence

PYGB
NM_002862.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.60

Publications

3 publications found

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]

PYGB links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.14276686).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002862.4. 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
	PYGB	NM_002862.4	MANE Select	c.88A>C	p.Lys30Gln	missense	Exon 1 of 20	NP_002853.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PYGB	ENST00000216962.9	TSL:1 MANE Select	c.88A>C	p.Lys30Gln	missense	Exon 1 of 20	ENSP00000216962.3	P11216
PYGB	ENST00000896654.1		c.88A>C	p.Lys30Gln	missense	Exon 1 of 21	ENSP00000566713.1
PYGB	ENST00000944638.1		c.88A>C	p.Lys30Gln	missense	Exon 1 of 21	ENSP00000614697.1

Frequencies

GnomAD3 genomes

AF:

0.000296

AC:

AN:

151880

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000967

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000589

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000308

AC:

AN:

237060

AF XY:

0.000240

show subpopulations

Gnomad AFR exome

AF:

0.0000695

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000636

Gnomad OTH exome

AF:

0.000354

GnomAD4 exome

AF:

0.000546

AC:

791

AN:

1448882

Hom.:

Cov.:

AF XY:

0.000545

AC XY:

393

AN XY:

720664

show subpopulations

African (AFR)

AF:

0.000186

AC:

AN:

32202

American (AMR)

AF:

0.00

AC:

AN:

42944

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25900

East Asian (EAS)

AF:

0.00

AC:

AN:

38474

South Asian (SAS)

AF:

0.0000355

AC:

AN:

84390

European-Finnish (FIN)

AF:

0.0000568

AC:

AN:

52814

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5742

European-Non Finnish (NFE)

AF:

0.000685

AC:

758

AN:

1106472

Other (OTH)

AF:

0.000350

AC:

AN:

59944

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

105

158

210

263

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

108

144

180

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000296

AC:

AN:

151992

Hom.:

Cov.:

AF XY:

0.000242

AC XY:

AN XY:

74312

show subpopulations

African (AFR)

AF:

0.0000964

AC:

AN:

41490

American (AMR)

AF:

0.0000654

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5102

South Asian (SAS)

AF:

0.00

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10578

Middle Eastern (MID)

AF:

0.00

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.000589

AC:

AN:

67932

Other (OTH)

AF:

0.00

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.518

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000502

Hom.:

Bravo

AF:

0.000400

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.000280

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.24

CADD

Benign

(source)

DANN

Benign

0.93

DEOGEN2

Uncertain

0.44

Eigen

Benign

-0.33

Eigen_PC

Benign

-0.24

FATHMM_MKL

Uncertain

0.81

LIST_S2

Uncertain

0.95

M_CAP

Pathogenic

0.47

MetaRNN

Benign

0.14

MetaSVM

Benign

-0.42

MutationAssessor

Benign

1.6

PhyloP100

1.6

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-1.9

REVEL

Benign

0.28

Sift

Benign

0.26

Sift4G

Benign

0.36

Polyphen

0.0

Vest4

0.29

MVP

0.84

MPC

0.22

ClinPred

0.042

GERP RS

1.6

PromoterAI

-0.17

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.42

gMVP

0.52

Mutation Taster

=68/32

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over