dbSNP rs16438: PYGB:c.*1308_*1312dupTGGGG (chr20-25297828-A-AGTGGG) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_002862.4(PYGB):c.*1308_*1312dupTGGGG variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.40 ( 13376 hom., cov: 0)

Exomes 𝑓: 0.37 ( 2 hom. )

Consequence

PYGB
NM_002862.4 3_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.328

Publications

11 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:

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]

ABHD12 Gene-Disease associations (from GenCC):

PHARC syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), PanelApp Australia, Orphanet, ClinGen

ABHD12 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.892 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PYGB	NM_002862.4 link	c.1308_1312dupTGGGG		3_prime_UTR_variant	Exon 20 of 20	ENST00000216962.9	NP_002853.2	P11216
ABHD12	NM_015600.5 link	c.1158-2803_1158-2799dupCCCAC		intron_variant	Intron 12 of 12		NP_056415.1	Q8N2K0-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PYGB	ENST00000216962.9 link	c.1308_1312dupTGGGG		3_prime_UTR_variant	Exon 20 of 20	1	NM_002862.4	ENSP00000216962.3		P11216

Frequencies

GnomAD3 genomes

AF:

0.404

AC:

61182

AN:

151552

Hom.:

13377

Cov.:

show subpopulations

Gnomad AFR

AF:

0.285

Gnomad AMI

AF:

0.510

Gnomad AMR

AF:

0.365

Gnomad ASJ

AF:

0.316

Gnomad EAS

AF:

0.914

Gnomad SAS

AF:

0.450

Gnomad FIN

AF:

0.448

Gnomad MID

AF:

0.379

Gnomad NFE

AF:

0.440

Gnomad OTH

AF:

0.386

GnomAD4 exome

AF:

0.367

AC:

AN:

Hom.:

Cov.:

AF XY:

0.273

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.333

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.639

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.403

AC:

61197

AN:

151672

Hom.:

13376

Cov.:

AF XY:

0.406

AC XY:

30098

AN XY:

74078

show subpopulations

African (AFR)

AF:

0.285

AC:

11802

AN:

41398

American (AMR)

AF:

0.364

AC:

5560

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.316

AC:

1094

AN:

3466

East Asian (EAS)

AF:

0.914

AC:

4672

AN:

5112

South Asian (SAS)

AF:

0.449

AC:

2157

AN:

4802

European-Finnish (FIN)

AF:

0.448

AC:

4709

AN:

10502

Middle Eastern (MID)

AF:

0.380

AC:

111

AN:

292

European-Non Finnish (NFE)

AF:

0.439

AC:

29813

AN:

67838

Other (OTH)

AF:

0.389

AC:

821

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

1768

3536

5303

7071

8839

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

586

1172

1758

2344

2930

<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:

0.413

Hom.:

1432

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.33

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over