NM_138387.4(G6PC3):c.778G>C (p.Gly260Arg) AND not provided

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Jan 3, 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:: RCV000986189.16

Allele description [Variation Report for NM_138387.4(G6PC3):c.778G>C (p.Gly260Arg)]

NM_138387.4(G6PC3):c.778G>C (p.Gly260Arg)

Gene:

G6PC3:glucose-6-phosphatase catalytic subunit 3 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

17q21.31

Genomic location:

Preferred name:

NM_138387.4(G6PC3):c.778G>C (p.Gly260Arg)

Other names:

G6PC3, GLY260ARG

HGVS:

NC_000017.11:g.44075780G>C
NG_015818.1:g.10051G>C
NM_001319945.2:c.*71G>C
NM_001384165.1:c.433G>C
NM_001384166.1:c.433G>C
NM_001384167.1:c.433G>C
NM_001384168.1:c.433G>C
NM_138387.4:c.778G>CMANE SELECT
NP_001371094.1:p.Gly145Arg
NP_001371095.1:p.Gly145Arg
NP_001371096.1:p.Gly145Arg
NP_001371097.1:p.Gly145Arg
NP_612396.1:p.Gly260Arg
NP_612396.1:p.Gly260Arg
NP_612396.1:p.Gly260Arg
LRG_182t1:c.778G>C
LRG_182:g.10051G>C
LRG_182p1:p.Gly260Arg
NC_000017.10:g.42153148G>C
NM_138387.3:c.778G>C
Q9BUM1:p.Gly260Arg

Protein change:

G145R; GLY260ARG

Links:

UniProtKB: Q9BUM1#VAR_064511; OMIM: 611045.0007; dbSNP: rs200478425

NCBI 1000 Genomes Browser:

rs200478425

Molecular consequence:

NM_001319945.2:c.*71G>C - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001384165.1:c.433G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001384166.1:c.433G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001384167.1:c.433G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001384168.1:c.433G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_138387.4:c.778G>C - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001135100	Mendelics	criteria provided, single submitter (Mendelics Assertion Criteria 2017)	Pathogenic (May 28, 2019)	unknown	clinical testing	Citation Link,
SCV001716318	Mayo Clinic Laboratories, Mayo Clinic	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jan 3, 2023)	germline	clinical testing	PubMed (10) [See all records that cite these PMIDs] 19118303, 19775295, 20220065, 20616219, 23180359, 23441086, 23758768, 25491320, 25492228, 25741868
SCV002571647	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Sep 10, 2022)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001135100

Mendelics

criteria provided, single submitter

(Mendelics Assertion Criteria 2017)

Pathogenic
(May 28, 2019)

unknown

clinical testing

Citation Link,

SCV001716318

Mayo Clinic Laboratories, Mayo Clinic

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Jan 3, 2023)

germline

clinical testing

PubMed (10)
[See all records that cite these PMIDs]

SCV002571647

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(Sep 10, 2022)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	2	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
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

A syndrome with congenital neutropenia and mutations in G6PC3.

Boztug K, Appaswamy G, Ashikov A, Schäffer AA, Salzer U, Diestelhorst J, Germeshausen M, Brandes G, Lee-Gossler J, Noyan F, Gatzke AK, Minkov M, Greil J, Kratz C, Petropoulou T, Pellier I, Bellanné-Chantelot C, Rezaei N, Mönkemöller K, Irani-Hakimeh N, Bakker H, Gerardy-Schahn R, et al.

N Engl J Med. 2009 Jan 1;360(1):32-43. doi: 10.1056/NEJMoa0805051. Erratum in: N Engl J Med. 2011 Apr 28;364(17):1682.

PubMed [citation]

PMID:: 19118303
PMCID:: PMC2778311

Prevalence of mutations in ELANE, GFI1, HAX1, SBDS, WAS and G6PC3 in patients with severe congenital neutropenia.

Xia J, Bolyard AA, Rodger E, Stein S, Aprikyan AA, Dale DC, Link DC.

Br J Haematol. 2009 Nov;147(4):535-42. doi: 10.1111/j.1365-2141.2009.07888.x. Epub 2009 Sep 22.

PubMed [citation]

PMID:: 19775295
PMCID:: PMC2783282

See all PubMed Citations (10)

Details of each submission

From Mendelics, SCV001135100.1

#	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 Mayo Clinic Laboratories, Mayo Clinic, SCV001716318.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	2	not provided	not provided	clinical testing	PubMed (10)

Description

PP1, PP3, PM3_very_strong, PS3_moderate, PS4

#	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		2	not provided	not provided	not provided

From GeneDx, SCV002571647.2

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

Description

Reported as a common pathogenic variant among individuals of European background (Banka and Newman, 2013); Published functional studies demonstrate a damaging effect with no detectable enzyme activity (Lin et al., 2015); Not observed at a significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 23441086, 19118303, 19775295, 20220065, 20616219, 23180359, 25491320, 23758768, 25492228)

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

Last Updated: Jun 2, 2024

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