rs7159068

Variant names:

• chr14-50904683-G-A
• rs7159068
• ENST00000382029.7:n.*1095G>A

Your query was ambiguous. Multiple possible variants found:

• chr14-50904683-G-A
• chr14-50904683-G-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000382029.7(ABHD12B):​n.*1095G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000147 in 272,340 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.000015 (0 hom.)
• Consequence: ABHD12B ENST00000382029.7 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0650
• Publications: 2 publications found

Genes affected

ABHD12B (HGNC:19837): (abhydrolase domain containing 12B) Predicted to enable acylglycerol lipase activity; lysophospholipase activity; and palmitoyl-(protein) hydrolase activity. Predicted to be involved in monoacylglycerol catabolic process and phosphatidylserine catabolic process. Predicted to be active in endoplasmic reticulum membrane. [provided by Alliance of Genome Resources, Apr 2022]

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]

PYGL Gene-Disease associations (from GenCC):

• glycogen storage disease VI

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, PanelApp Australia, Genomics England PanelApp, Orphanet, Ambry Genetics

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABHD12B	NM_001206673.2	c.*317G>A		3_prime_UTR_variant	Exon 13 of 13	ENST00000337334.7	NP_001193602.1
ABHD12B	NM_181814.2	c.*317G>A		3_prime_UTR_variant	Exon 11 of 11		NP_861535.1
ABHD12B	NM_181533.4	c.*317G>A		3_prime_UTR_variant	Exon 12 of 12		NP_853511.2
ABHD12B	XM_011536474.3	c.*317G>A		3_prime_UTR_variant	Exon 13 of 13		XP_011534776.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABHD12B	ENST00000337334.7	c.*317G>A		3_prime_UTR_variant	Exon 13 of 13	1	NM_001206673.2	ENSP00000336693.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000147 AC: 4 AN: 272340 Hom.: 0 Cov.: 0 AF XY: 0.0000277 AC XY: 4 AN XY: 144222

African (AFR) AF: 0.000113 AC: 1 AN: 8862

American (AMR) AF: 0.00 AC: 0 AN: 12598

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 8338

East Asian (EAS) AF: 0.00 AC: 0 AN: 16400

South Asian (SAS) AF: 0.00 AC: 0 AN: 31988

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 13404

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1156

European-Non Finnish (NFE) AF: 0.0000183 AC: 3 AN: 163910

Other (OTH) AF: 0.00 AC: 0 AN: 15684

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 56

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.7
DANN	Benign	0.64
PhyloP100		0.065

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

Other links and lift over

dbSNP: rs7159068; hg19: chr14-51371401;