NM_000642.3(AGL):c.293+3A>G AND Glycogen storage disease type III

Clinical significance:Conflicting interpretations of pathogenicity, Likely benign(1);Uncertain significance(1) (Last evaluated: Jul 15, 2021)

Review status:1 star out of maximum of 4 stars

criteria provided, conflicting interpretations

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000686891.3

Allele description [Variation Report for NM_000642.3(AGL):c.293+3A>G]

NM_000642.3(AGL):c.293+3A>G

Gene:
AGL:amylo-alpha-1, 6-glucosidase, 4-alpha-glucanotransferase [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
1p21.2
Genomic location:
Preferred name:
NM_000642.3(AGL):c.293+3A>G
HGVS:
  • NC_000001.11:g.99861716A>G
  • NG_012865.1:g.16633A>G
  • NM_000028.2:c.293+3A>G
  • NM_000642.3:c.293+3A>GMANE SELECT
  • NM_000643.2:c.293+3A>G
  • NM_000644.2:c.293+3A>G
  • NM_000646.2:c.245+3A>G
  • NC_000001.10:g.100327272A>G
  • NM_000642.2:c.293+3A>G
Links:
dbSNP: rs375459662
NCBI 1000 Genomes Browser:
rs375459662
Molecular consequence:
  • NM_000028.2:c.293+3A>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000642.3:c.293+3A>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000643.2:c.293+3A>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000644.2:c.293+3A>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000646.2:c.245+3A>G - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Name:
Glycogen storage disease type III (GSD3)
Synonyms:
Glycogen storage disease type 3; Forbes disease; Cori disease; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0009291; MedGen: C0017922; Orphanet: 366; OMIM: 232400

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000814432Invitaecriteria provided, single submitter
Uncertain significance
(Oct 23, 2018)
germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

SCV002055517Nilou-Genome Labcriteria provided, single submitter
Likely benign
(Jul 15, 2021)
germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Summary from all submissions

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

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From Invitae, SCV000814432.2

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

Description

This sequence change falls in intron 3 of the AGL gene. It does not directly change the encoded amino acid sequence of the AGL protein, but it affects a nucleotide within the consensus splice site of the intron. This variant is present in population databases (rs375459662, ExAC 0.01%). This variant has not been reported in the literature in individuals with AGL-related disease. Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing, but this prediction has not been confirmed by published transcriptional studies. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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

From Nilou-Genome Lab, SCV002055517.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenonot providednot providednot providednot providednot providednot providednot provided

Last Updated: Jan 12, 2022

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