rs7142143

Positions:

• chr14-50936813-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002863.5(PYGL):​c.345+923A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0266 in 151,264 control chromosomes in the GnomAD database, including 171 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.027 (171 hom., cov: 32)
• Consequence: PYGL NM_002863.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0530

Genes affected

PYGL (HGNC:9725): (glycogen phosphorylase L) This gene encodes a homodimeric protein that catalyses the cleavage of alpha-1,4-glucosidic bonds to release glucose-1-phosphate from liver glycogen stores. This protein switches from inactive phosphorylase B to active phosphorylase A by phosphorylation of serine residue 15. Activity of this enzyme is further regulated by multiple allosteric effectors and hormonal controls. Humans have three glycogen phosphorylase genes that encode distinct isozymes that are primarily expressed in liver, brain and muscle, respectively. The liver isozyme serves the glycemic demands of the body in general while the brain and muscle isozymes supply just those tissues. In glycogen storage disease type VI, also known as Hers disease, mutations in liver glycogen phosphorylase inhibit the conversion of glycogen to glucose and results in moderate hypoglycemia, mild ketosis, growth retardation and hepatomegaly. Alternative splicing results in multiple transcript variants encoding different isoforms.[provided by RefSeq, Feb 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0907 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PYGL	NM_002863.5	c.345+923A>G		intron_variant		ENST00000216392.8	NP_002854.3
PYGL	NM_001163940.2	c.244-1628A>G		intron_variant			NP_001157412.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PYGL	ENST00000216392.8	c.345+923A>G		intron_variant		1	NM_002863.5	ENSP00000216392	P1
PYGL	ENST00000532462.5	c.345+923A>G		intron_variant		1		ENSP00000431657
PYGL	ENST00000530336.2	n.412+923A>G		intron_variant, non_coding_transcript_variant		1
PYGL	ENST00000544180.6	c.244-1628A>G		intron_variant		2		ENSP00000443787

Frequencies

GnomAD3 genomes AF: 0.0265 AC: 4012 AN: 151170 Hom.: 170 Cov.: 32

Gnomad AFR AF: 0.0930

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00870

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000265

Gnomad OTH AF: 0.0192

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0266 AC: 4026 AN: 151264 Hom.: 171 Cov.: 32 AF XY: 0.0259 AC XY: 1912 AN XY: 73788

Gnomad4 AFR AF: 0.0932

Gnomad4 AMR AF: 0.00862

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000209

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000265

Gnomad4 OTH AF: 0.0190

Alfa AF: 0.00949 Hom.: 14

Bravo AF: 0.0298

Asia WGS AF: 0.00347 AC: 12 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.2
DANN	Benign	0.49

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: rs7142143; hg19: chr14-51403531;