NM_001206673.2:c.422T>C

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_001206673.2(ABHD12B):c.422T>C(p.Ile141Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000685 in 1,606,700 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

ABHD12B
NM_001206673.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.47

Publications

1 publications found

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 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

PYGL links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.827

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ABHD12B	NM_001206673.2	MANE Select	c.422T>C	p.Ile141Thr	missense	Exon 4 of 13	NP_001193602.1	Q7Z5M8-1
ABHD12B	NM_181814.2		c.191T>C	p.Ile64Thr	missense	Exon 2 of 11	NP_861535.1	Q7Z5M8-2
ABHD12B	NM_181533.4		c.101T>C	p.Ile34Thr	missense	Exon 3 of 12	NP_853511.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ABHD12B	ENST00000337334.7	TSL:1 MANE Select	c.422T>C	p.Ile141Thr	missense	Exon 4 of 13	ENSP00000336693.2	Q7Z5M8-1
ABHD12B	ENST00000353130.5	TSL:1	c.191T>C	p.Ile64Thr	missense	Exon 2 of 11	ENSP00000343951.1	Q7Z5M8-2
PYGL	ENST00000532462.5	TSL:1	c.2380-22369A>G		intron	N/A	ENSP00000431657.1	E9PK47

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000816

AC:

AN:

244962

AF XY:

0.0000151

show subpopulations

Gnomad AFR exome

AF:

0.000127

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000275

AC:

AN:

1454434

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

723532

show subpopulations

African (AFR)

AF:

0.0000907

AC:

AN:

33070

American (AMR)

AF:

0.00

AC:

AN:

43902

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25992

East Asian (EAS)

AF:

0.00

AC:

AN:

39020

South Asian (SAS)

AF:

0.00

AC:

AN:

85212

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53280

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5750

European-Non Finnish (NFE)

AF:

9.02e-7

AC:

AN:

1108172

Other (OTH)

AF:

0.00

AC:

AN:

60036

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152266

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74456

show subpopulations

African (AFR)

AF:

0.000168

AC:

AN:

41550

American (AMR)

AF:

0.00

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68006

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.417

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000264

ExAC

AF:

0.00000824

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.65

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.22

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.057

Eigen

Benign

0.076

Eigen_PC

Benign

0.047

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.89

M_CAP

Benign

0.022

MetaRNN

Pathogenic

0.83

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.96

PhyloP100

7.5

PrimateAI

Benign

0.48

PROVEAN

Uncertain

-3.9

REVEL

Uncertain

0.38

Sift

Uncertain

0.0010

Sift4G

Benign

0.079

Polyphen

1.0

Vest4

0.73

MutPred

0.54

Gain of catalytic residue at R136 (P = 8e-04)

MVP

0.49

MPC

0.37

ClinPred

0.95

GERP RS

5.5

Varity_R

0.54

gMVP

0.69

Mutation Taster

=84/16

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over