NM_000170.3(GLDC):c.1342G>T (p.Glu448Ter) AND Non-ketotic hyperglycinemia

Germline classification:: Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:: Feb 7, 2022
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:: RCV000669887.3

Allele description [Variation Report for NM_000170.3(GLDC):c.1342G>T (p.Glu448Ter)]

NM_000170.3(GLDC):c.1342G>T (p.Glu448Ter)

Gene:

GLDC:glycine decarboxylase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

9p24.1

Genomic location:

Preferred name:

NM_000170.3(GLDC):c.1342G>T (p.Glu448Ter)

HGVS:

NC_000009.12:g.6592910C>A
NG_016397.1:g.57783G>T
NM_000170.3:c.1342G>TMANE SELECT
NP_000161.2:p.Glu448Ter
NP_000161.2:p.Glu448Ter
LRG_643t1:c.1342G>T
LRG_643:g.57783G>T
LRG_643p1:p.Glu448Ter
NC_000009.11:g.6592910C>A
NM_000170.2:c.1342G>T

Protein change:

E448*

Links:

dbSNP: rs777365335

NCBI 1000 Genomes Browser:

rs777365335

Molecular consequence:

NM_000170.3:c.1342G>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Non-ketotic hyperglycinemia
Synonyms:: Glycine encephalopathy; Nonketotic hyperglycinemia
Identifiers:: MONDO: MONDO:0011612; MedGen: C0751748; Orphanet: 407; OMIM: PS605899; Human Phenotype Ontology: HP:0008288

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TSA: Sus scrofa CUFF.111958.1 transcribed RNA sequence
TSA: Sus scrofa CUFF.111958.1 transcribed RNA sequence
gb|GFLN01128930.1||gnl|TSA:GFLN01|C 11958.1

Nucleotide
Mycoplasma pneumoniae DNA, complete genome, strain: KCH-402
Mycoplasma pneumoniae DNA, complete genome, strain: KCH-402
gi|1041923298|dbj|AP017318.1|

Nucleotide
RsmZ (493)
Nucleotide
Homo sapiens ABCB6 gene, note: Lan-null 2383-2385del
Homo sapiens ABCB6 gene, note: Lan-null 2383-2385del
gi|521969577|dbj|AB829907.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000794683	Counsyl	criteria provided, single submitter (Counsyl Autosomal Recessive and X-Linked Classification Criteria (2018))	Likely pathogenic (Oct 11, 2017)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link,
SCV003441361	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Feb 7, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 27362913, 16601880, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000794683

Counsyl

criteria provided, single submitter

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

Likely pathogenic
(Oct 11, 2017)

unknown

clinical testing

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

Citation Link,

SCV003441361

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Feb 7, 2022)

germline

clinical testing

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

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

The genetic basis of classic nonketotic hyperglycinemia due to mutations in GLDC and AMT.

Coughlin CR 2nd, Swanson MA, Kronquist K, Acquaviva C, Hutchin T, Rodríguez-Pombo P, Väisänen ML, Spector E, Creadon-Swindell G, Brás-Goldberg AM, Rahikkala E, Moilanen JS, Mahieu V, Matthijs G, Bravo-Alonso I, Pérez-Cerdá C, Ugarte M, Vianey-Saban C, Scharer GH, Van Hove JL.

Genet Med. 2017 Jan;19(1):104-111. doi: 10.1038/gim.2016.74. Epub 2016 Jun 30. Erratum in: Genet Med. 2018 Sep;20(9):1098. doi: 10.1038/gim.2017.232.

PubMed [citation]

PMID:: 27362913

Genetic heterogeneity of the GLDC gene in 28 unrelated patients with glycine encephalopathy.

Conter C, Rolland MO, Cheillan D, Bonnet V, Maire I, Froissart R.

J Inherit Metab Dis. 2006 Feb;29(1):135-42.

PubMed [citation]

PMID:: 16601880

See all PubMed Citations (3)

Details of each submission

From Counsyl, SCV000794683.1

#	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

From Invitae, SCV003441361.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

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 create or strengthen a splice site. ClinVar contains an entry for this variant (Variation ID: 554282). This premature translational stop signal has been observed in individual(s) with GLDC-related conditions (PMID: 27362913). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Glu448*) in the GLDC gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in GLDC are known to be pathogenic (PMID: 16601880).

#	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: Jun 9, 2024

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