14-50904683-G-T

Position:

• chr14-50904683-G-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABHD12B	NM_001206673.2	c.*317G>T		3_prime_UTR_variant	13/13	ENST00000337334.7
ABHD12B	NM_181533.4	c.*317G>T		3_prime_UTR_variant	12/12
ABHD12B	NM_181814.2	c.*317G>T		3_prime_UTR_variant	11/11
ABHD12B	XM_011536474.3	c.*317G>T		3_prime_UTR_variant	13/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABHD12B	ENST00000337334.7	c.*317G>T		3_prime_UTR_variant	13/13	1	NM_001206673.2	P1

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

Gnomad4 AFR exome AF: 0.0577

Gnomad4 AMR exome AF: 0.0529

Gnomad4 ASJ exome AF: 0.0131

Gnomad4 EAS exome AF: 0.0674

Gnomad4 SAS exome AF: 0.0305

Gnomad4 FIN exome AF: 0.0224

Gnomad4 NFE exome AF: 0.0183

Gnomad4 OTH exome AF: 0.0290

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

Gnomad4 AFR AF: 0.0581

Gnomad4 AMR AF: 0.0516

Gnomad4 ASJ AF: 0.0118

Gnomad4 EAS AF: 0.0586

Gnomad4 SAS AF: 0.0340

Gnomad4 FIN AF: 0.0207

Gnomad4 NFE AF: 0.0186

Gnomad4 OTH AF: 0.0340

Alfa AF: 0.0217 Hom.: 21

Bravo AF: 0.0377

Asia WGS AF: 0.0490 AC: 171 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.6
DANN	Benign	0.64

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: rs7159068; hg19: chr14-51371401; COSMIC: COSV99369219; COSMIC: COSV99369219;