14-50904683-G-T

Variant names:

• chr14-50904683-G-T
• rs7159068
• NM_001206673.2:c.*317G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001206673.2(ABHD12B):​c.*317G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0292 in 424,484 control chromosomes in the GnomAD database, including 283 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 0.035 (128 hom., cov: 32)
  • Exomes 𝑓: 0.026 (155 hom.)
• Consequence: ABHD12B NM_001206673.2 3_prime_UTR
• 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: G2P, Genomics England PanelApp, ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0561 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001206673.2. 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
	ABHD12B	NM_001206673.2	MANE Select	c.*317G>T		3_prime_UTR	Exon 13 of 13	NP_001193602.1	Q7Z5M8-1
	ABHD12B	NM_181814.2		c.*317G>T		3_prime_UTR	Exon 11 of 11	NP_861535.1	Q7Z5M8-2
	ABHD12B	NM_181533.4		c.*317G>T		3_prime_UTR	Exon 12 of 12	NP_853511.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABHD12B	ENST00000337334.7	TSL:1 MANE Select	c.*317G>T		3_prime_UTR	Exon 13 of 13	ENSP00000336693.2	Q7Z5M8-1
	ABHD12B	ENST00000353130.5	TSL:1	c.*317G>T		3_prime_UTR	Exon 11 of 11	ENSP00000343951.1	Q7Z5M8-2
	PYGL	ENST00000532462.5	TSL:1	c.2379+3588C>A		intron	N/A	ENSP00000431657.1	E9PK47

Frequencies

GnomAD3 genomes AF: 0.0346 AC: 5258 AN: 152178 Hom.: 126 Cov.: 32

Gnomad AFR AF: 0.0578

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0516

Gnomad ASJ AF: 0.0118

Gnomad EAS AF: 0.0587

Gnomad SAS AF: 0.0338

Gnomad FIN AF: 0.0207

Gnomad MID AF: 0.0223

Gnomad NFE AF: 0.0186

Gnomad OTH AF: 0.0344

GnomAD4 exome AF: 0.0262 AC: 7125 AN: 272188 Hom.: 155 Cov.: 0 AF XY: 0.0261 AC XY: 3757 AN XY: 144130

African (AFR) AF: 0.0577 AC: 511 AN: 8854

American (AMR) AF: 0.0529 AC: 666 AN: 12582

Ashkenazi Jewish (ASJ) AF: 0.0131 AC: 109 AN: 8336

East Asian (EAS) AF: 0.0674 AC: 1104 AN: 16386

South Asian (SAS) AF: 0.0305 AC: 976 AN: 31956

European-Finnish (FIN) AF: 0.0224 AC: 300 AN: 13394

Middle Eastern (MID) AF: 0.0104 AC: 12 AN: 1156

European-Non Finnish (NFE) AF: 0.0183 AC: 2992 AN: 163848

Other (OTH) AF: 0.0290 AC: 455 AN: 15676

GnomAD4 genome AF: 0.0346 AC: 5273 AN: 152296 Hom.: 128 Cov.: 32 AF XY: 0.0359 AC XY: 2671 AN XY: 74466

African (AFR) AF: 0.0581 AC: 2414 AN: 41574

American (AMR) AF: 0.0516 AC: 789 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0118 AC: 41 AN: 3472

East Asian (EAS) AF: 0.0586 AC: 304 AN: 5184

South Asian (SAS) AF: 0.0340 AC: 164 AN: 4824

European-Finnish (FIN) AF: 0.0207 AC: 220 AN: 10608

Middle Eastern (MID) AF: 0.0171 AC: 5 AN: 292

European-Non Finnish (NFE) AF: 0.0186 AC: 1263 AN: 68010

Other (OTH) AF: 0.0340 AC: 72 AN: 2116

Alfa AF: 0.0260 Hom.: 56

Bravo AF: 0.0377

Asia WGS AF: 0.0490 AC: 171 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.6
DANN	Benign	0.64
PhyloP100		0.065
Mutation Taster		=100/0	polymorphism (auto)

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; COSMIC: COSV99369219; COSMIC: COSV99369219;