NM_000151.4(G6PC1):c.1036G>A (p.Ala346Thr) AND Glycogen storage disease due to glucose-6-phosphatase deficiency type IA

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Nov 14, 2023
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV003118135.5

Allele description [Variation Report for NM_000151.4(G6PC1):c.1036G>A (p.Ala346Thr)]

NM_000151.4(G6PC1):c.1036G>A (p.Ala346Thr)

Gene:

G6PC1:glucose-6-phosphatase catalytic subunit 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

17q21.31

Genomic location:

Preferred name:

NM_000151.4(G6PC1):c.1036G>A (p.Ala346Thr)

HGVS:

NC_000017.11:g.42911388G>A
NG_011808.1:g.15591G>A
NM_000151.4:c.1036G>AMANE SELECT
NM_001270397.2:c.*428G>A
NP_000142.1:p.Ala346Thr
NP_000142.2:p.Ala346Thr
LRG_147t1:c.1036G>A
LRG_147:g.15591G>A
LRG_147p1:p.Ala346Thr
NC_000017.10:g.41063405G>A
NM_000151.2:c.1036G>A

Protein change:

A346T

Molecular consequence:

NM_001270397.2:c.*428G>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_000151.4:c.1036G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Glycogen storage disease due to glucose-6-phosphatase deficiency type IA (GSD1A)
Synonyms:: GSD Ia; Glycogen storage disease type 1A; Von Gierke disease; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0009287; MedGen: C2919796; Orphanet: 364; Orphanet: 79258; OMIM: 232200

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PACS1 phosphofurin acidic cluster sorting protein 1 [Homo sapiens]
PACS1 phosphofurin acidic cluster sorting protein 1 [Homo sapiens]
Gene ID:55690

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Dguok deoxyguanosine kinase [Rattus norvegicus]
Dguok deoxyguanosine kinase [Rattus norvegicus]
Gene ID:297389

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Gene Links for GEO Profiles (Select 65265682) (1)
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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003784286	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Nov 14, 2023)	germline	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

SCV003784286

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Nov 14, 2023)

germline

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

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

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003784286.3

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

Description

This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 346 of the G6PC protein (p.Ala346Thr). This variant is present in population databases (no rsID available, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with G6PC-related conditions. ClinVar contains an entry for this variant (Variation ID: 2418026). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt G6PC protein function with a positive predictive value of 80%. 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.

#	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

Last Updated: Sep 29, 2024

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