NM_000642.3(AGL):c.664+3A>G AND Glycogen storage disease IIIa

Clinical significance:Pathogenic (Last evaluated: Apr 21, 2017)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:

Allele description [Variation Report for NM_000642.3(AGL):c.664+3A>G]


AGL:amylo-alpha-1, 6-glucosidase, 4-alpha-glucanotransferase [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Genomic location:
Preferred name:
  • NC_000001.11:g.99864592A>G
  • NG_012865.1:g.19509A>G
  • NM_000028.2:c.664+3A>G
  • NM_000642.3:c.664+3A>GMANE SELECT
  • NM_000643.2:c.664+3A>G
  • NM_000644.2:c.664+3A>G
  • NM_000646.2:c.616+3A>G
  • NC_000001.10:g.100330148A>G
  • NM_000642.2:c.664+3A>G
dbSNP: rs370792293
NCBI 1000 Genomes Browser:
Molecular consequence:
  • NM_000028.2:c.664+3A>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000642.3:c.664+3A>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000643.2:c.664+3A>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000644.2:c.664+3A>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000646.2:c.616+3A>G - intron variant - [Sequence Ontology: SO:0001627]


Glycogen storage disease IIIa (GSD IIIa)
MedGen: C1968739

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
SCV000697535Women's Health and Genetics/Laboratory Corporation of America, LabCorpcriteria provided, single submitter
(Apr 21, 2017)
germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

LabCorp Variant Classification Summary - May 2015.docx

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing



Molecular characterisation of GSD III subjects and identification of six novel mutations in AGL.

Lucchiari S, Donati MA, Parini R, Melis D, Gatti R, Bresolin N, Scarlato G, Comi GP.

Hum Mutat. 2002 Dec;20(6):480.

PubMed [citation]

Molecular diagnosis of glycogen storage disease and disorders with overlapping clinical symptoms by massive parallel sequencing.

Vega AI, Medrano C, Navarrete R, Desviat LR, Merinero B, Rodríguez-Pombo P, Vitoria I, Ugarte M, Pérez-Cerdá C, Pérez B.

Genet Med. 2016 Oct;18(10):1037-43. doi: 10.1038/gim.2015.217. Epub 2016 Feb 25.

PubMed [citation]
See all PubMed Citations (3)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000697535.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)


Variant summary: The AGL c.664+3A>G variant is an intronic change that involves a conserved nucleotide. 3/5 splice prediction tools predict an impact on normal splicing, which was confirmed by Lucchiar_2002. The cDNA analysis revealed found an in-frame deletion of exon 6 caused by the variant of interest, and, as confirmation, all homozygous patients showed no enzymatic residual activity. This variant was found in 2/120192 control chromosomes at a frequency of 0.0000166, which does not exceed the estimated maximal expected allele frequency of a pathogenic AGL variant (0.0022822). The variant was identified in multiple GSD III patients homozygously or in compound heterozygosity. Lastly, a clinical diagnostic laboratory classifies the variant as "likely pathogenic." Taking together, the variant of interest has been classified as "pathogenic."

OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Aug 27, 2021

Support Center