NM_000642.3(AGL):c.1159C>T (p.Arg387Ter) AND Glycogen storage disease type III

Germline classification:: Pathogenic/Likely pathogenic (3 submissions)
Last evaluated:: Nov 14, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000669251.4

Allele description [Variation Report for NM_000642.3(AGL):c.1159C>T (p.Arg387Ter)]

NM_000642.3(AGL):c.1159C>T (p.Arg387Ter)

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.1159C>T (p.Arg387Ter)

HGVS:

NC_000001.11:g.99875230C>T
NG_012865.1:g.30147C>T
NM_000028.3:c.1159C>T
NM_000642.3:c.1159C>TMANE SELECT
NM_000643.3:c.1159C>T
NM_000644.3:c.1159C>T
NM_000646.3:c.1111C>T
NM_001425325.1:c.1159C>T
NM_001425326.1:c.1159C>T
NM_001425328.1:c.955C>T
NM_001425329.1:c.955C>T
NM_001425332.1:c.781C>T
NP_000019.2:p.Arg387Ter
NP_000019.2:p.Arg387Ter
NP_000633.2:p.Arg387Ter
NP_000634.2:p.Arg387Ter
NP_000634.2:p.Arg387Ter
NP_000635.2:p.Arg387Ter
NP_000635.2:p.Arg387Ter
NP_000637.2:p.Arg371Ter
NP_000637.2:p.Arg371Ter
NP_001412254.1:p.Arg387Ter
NP_001412255.1:p.Arg387Ter
NP_001412257.1:p.Arg319Ter
NP_001412258.1:p.Arg319Ter
NP_001412261.1:p.Arg261Ter
NC_000001.10:g.100340786C>T
NM_000028.2:c.1159C>T
NM_000642.2:c.1159C>T
NM_000643.2:c.1159C>T
NM_000644.2:c.1159C>T
NM_000646.2:c.1111C>T

Protein change:

R261*

Links:

dbSNP: rs1553185418

NCBI 1000 Genomes Browser:

rs1553185418

Molecular consequence:

NM_000028.3:c.1159C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_000642.3:c.1159C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_000643.3:c.1159C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_000644.3:c.1159C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_000646.3:c.1111C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001425325.1:c.1159C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001425326.1:c.1159C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001425328.1:c.955C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001425329.1:c.955C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001425332.1:c.781C>T - nonsense - [Sequence Ontology: SO:0001587]

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

Recent activity

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peptidylprolyl isomerase [Globicatella sp. HMSC072A10]
peptidylprolyl isomerase [Globicatella sp. HMSC072A10]
gi|1100842227|ref|WP_071408101.1|

Protein
acetylxylan esterase [Globicatella sp. HMSC072A10]
acetylxylan esterase [Globicatella sp. HMSC072A10]
gi|1100842705|ref|WP_071408579.1|

Protein
group II intron maturase-specific domain-containing protein, partial [Globicatel...
group II intron maturase-specific domain-containing protein, partial [Globicatella sp. HMSC072A10]
gi|2562832923|ref|WP_305793928.1|

Protein
Listeria monocytogenes
Listeria monocytogenes
GenomeTrakr project: FDA-CFSAN, IFSH

BioProject
PREDICTED: Otolemur garnettii dehydrodolichyl diphosphate synthase subunit (DHDD...
PREDICTED: Otolemur garnettii dehydrodolichyl diphosphate synthase subunit (DHDDS), mRNA
gi|1327817556|ref|XM_012811396.2|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000793985	Counsyl	criteria provided, single submitter (Counsyl Autosomal Recessive and X-Linked Classification Criteria (2018))	Likely pathogenic (Sep 6, 2017)	unknown	clinical testing	Citation Link,
SCV004373499	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (May 22, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 19299494, 28492532
SCV005058504	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Nov 14, 2023)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000793985

Counsyl

criteria provided, single submitter

(Counsyl Autosomal Recessive and X-Linked Classification Criteria (2018))

Likely pathogenic
(Sep 6, 2017)

unknown

clinical testing

Citation Link,

SCV004373499

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(May 22, 2023)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

SCV005058504

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Nov 14, 2023)

unknown

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Distinct mutations in the glycogen debranching enzyme found in glycogen storage disease type III lead to impairment in diverse cellular functions.

Cheng A, Zhang M, Okubo M, Omichi K, Saltiel AR.

Hum Mol Genet. 2009 Jun 1;18(11):2045-52. doi: 10.1093/hmg/ddp128. Epub 2009 Mar 19.

PubMed [citation]

PMID:: 19299494
PMCID:: PMC2678930

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. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

See all PubMed Citations (3)

Details of each submission

From Counsyl, SCV000793985.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004373499.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 553738). This variant has not been reported in the literature in individuals affected with AGL-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Arg387*) in the AGL gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in AGL are known to be pathogenic (PMID: 19299494).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Baylor Genetics, SCV005058504.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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