Genetic Variant ABHD12B:c.*317G>T (chr14-50904683-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0650

Variant links:

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]

ABHD12B links:

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 links:

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ACMG classification

Classification made for transcript

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	Effect	Exon rank	MANE	Protein	UniProt
ABHD12B	NM_001206673.2 link	c.*317G>T	3_prime_UTR_variant	Exon 13 of 13	ENST00000337334.7	NP_001193602.1	Q7Z5M8-1
ABHD12B	NM_181814.2 link	c.*317G>T	3_prime_UTR_variant	Exon 11 of 11		NP_861535.1	Q7Z5M8-2
ABHD12B	NM_181533.4 link	c.*317G>T	3_prime_UTR_variant	Exon 12 of 12		NP_853511.2	Q7Z5M8
ABHD12B	XM_011536474.3 link	c.*317G>T	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 link	c.*317G>T		3_prime_UTR_variant	Exon 13 of 13	1	NM_001206673.2	ENSP00000336693.2		Q7Z5M8-1

Frequencies

GnomAD3 genomes

AF:

0.0346

AC:

5258

AN:

152178

Hom.:

126

Cov.:

show subpopulations

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.:

AF XY:

0.0261

AC XY:

3757

AN XY:

144130

show subpopulations

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.:

AF XY:

0.0359

AC XY:

2671

AN XY:

74466

show subpopulations

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.:

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over