rs16438

Positions:

• chr20-25297828-A-AGTGGG

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_002862.4(PYGB):​c.*1308_*1312dup 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.328

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 Benign. Variant got -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/exons	MANE	Protein	UniProt
PYGB	NM_002862.4	c.*1308_*1312dup		3_prime_UTR_variant	20/20	ENST00000216962.9	NP_002853.2
ABHD12	NM_015600.5	c.1158-2799_1158-2798insCCCAC		intron_variant			NP_056415.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PYGB	ENST00000216962.9	c.*1308_*1312dup		3_prime_UTR_variant	20/20	1	NM_002862.4	ENSP00000216962	P1

Frequencies

GnomAD3 genomes AF: 0.404 AC: 61182 AN: 151552 Hom.: 13377 Cov.: 0

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: 11 AN: 30 Hom.: 2 Cov.: 0 AF XY: 0.273 AC XY: 6 AN XY: 22

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.333

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.403 AC: 61197 AN: 151672 Hom.: 13376 Cov.: 0 AF XY: 0.406 AC XY: 30098 AN XY: 74078

Gnomad4 AFR AF: 0.285

Gnomad4 AMR AF: 0.364

Gnomad4 ASJ AF: 0.316

Gnomad4 EAS AF: 0.914

Gnomad4 SAS AF: 0.449

Gnomad4 FIN AF: 0.448

Gnomad4 NFE AF: 0.439

Gnomad4 OTH AF: 0.389

Alfa AF: 0.413 Hom.: 1432

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs16438; hg19: chr20-25278464;