GeneBe

rs754606378

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_000642.3(AGL):​c.1552A>C​(p.Thr518Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T518A) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Consequence

AGL
NM_000642.3 missense

Scores

1
10
7

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.65

Publications

0 publications found
Variant links:
Genes affected
AGL (HGNC:321): (amylo-alpha-1, 6-glucosidase, 4-alpha-glucanotransferase) This gene encodes the glycogen debrancher enzyme which is involved in glycogen degradation. This enzyme has two independent catalytic activities which occur at different sites on the protein: a 4-alpha-glucotransferase activity and a amylo-1,6-glucosidase activity. Mutations in this gene are associated with glycogen storage disease although a wide range of enzymatic and clinical variability occurs which may be due to tissue-specific alternative splicing. Alternatively spliced transcripts encoding different isoforms have been described. [provided by RefSeq, Jul 2008]
AGL Gene-Disease associations (from GenCC):
  • glycogen storage disease III
    Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Ambry Genetics, Laboratory for Molecular Medicine, Myriad Women’s Health, Orphanet, G2P, PanelApp Australia, Labcorp Genetics (formerly Invitae), Genomics England PanelApp

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000642.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
AGL
NM_000642.3
MANE Select
c.1552A>Cp.Thr518Pro
missense
Exon 12 of 34NP_000633.2
AGL
NM_000028.3
c.1552A>Cp.Thr518Pro
missense
Exon 12 of 34NP_000019.2
AGL
NM_000643.3
c.1552A>Cp.Thr518Pro
missense
Exon 12 of 34NP_000634.2

Ensembl Transcripts

Selected
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
AGL
ENST00000361915.8
TSL:1 MANE Select
c.1552A>Cp.Thr518Pro
missense
Exon 12 of 34ENSP00000355106.3
AGL
ENST00000294724.8
TSL:1
c.1552A>Cp.Thr518Pro
missense
Exon 12 of 34ENSP00000294724.4
AGL
ENST00000370163.7
TSL:1
c.1552A>Cp.Thr518Pro
missense
Exon 12 of 34ENSP00000359182.3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.32
BayesDel_addAF
Pathogenic
0.21
D
BayesDel_noAF
Uncertain
0.070
CADD
Uncertain
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.11
T
Eigen
Benign
0.15
Eigen_PC
Uncertain
0.31
FATHMM_MKL
Uncertain
0.91
D
LIST_S2
Uncertain
0.92
D
M_CAP
Benign
0.051
D
MetaRNN
Uncertain
0.47
T
MetaSVM
Uncertain
-0.19
T
MutationAssessor
Benign
1.8
L
PhyloP100
5.6
PrimateAI
Benign
0.44
T
PROVEAN
Benign
-0.80
N
REVEL
Uncertain
0.40
Sift
Uncertain
0.015
D
Sift4G
Uncertain
0.0080
D
Polyphen
0.31
B
Vest4
0.58
MutPred
0.41
Gain of catalytic residue at T518 (P = 0.015)
MVP
0.89
MPC
0.071
ClinPred
0.84
D
GERP RS
5.9
Varity_R
0.37
gMVP
0.72
Mutation Taster
=83/17
polymorphism

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.10
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs754606378; hg19: chr1-100343325; API