NM_006623.4(PHGDH):c.403C>G (p.Arg135Gly) AND PHGDH deficiency

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Nov 2, 2021
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:: RCV002904904.2

Allele description [Variation Report for NM_006623.4(PHGDH):c.403C>G (p.Arg135Gly)]

NM_006623.4(PHGDH):c.403C>G (p.Arg135Gly)

Gene:

PHGDH:phosphoglycerate dehydrogenase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1p12

Genomic location:

Preferred name:

NM_006623.4(PHGDH):c.403C>G (p.Arg135Gly)

HGVS:

NC_000001.11:g.119726897C>G
NG_009188.1:g.20102C>G
NM_006623.4:c.403C>GMANE SELECT
NP_006614.2:p.Arg135Gly
NC_000001.10:g.120269520C>G

Protein change:

R135G

Molecular consequence:

NM_006623.4:c.403C>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: PHGDH deficiency
Synonyms:: Phosphoglycerate dehydrogenase deficiency
Identifiers:: MONDO: MONDO:0011152; MedGen: C1866174; OMIM: 601815

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003260055	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Nov 2, 2021)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 19235232, 26610677, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003260055

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Nov 2, 2021)

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

Citations

PubMed

Novel mutations in 3-phosphoglycerate dehydrogenase (PHGDH) are distributed throughout the protein and result in altered enzyme kinetics.

Tabatabaie L, de Koning TJ, Geboers AJ, van den Berg IE, Berger R, Klomp LW.

Hum Mutat. 2009 May;30(5):749-56. doi: 10.1002/humu.20934.

PubMed [citation]

PMID:: 19235232

Two new cases of serine deficiency disorders treated with l-serine.

Brassier A, Valayannopoulos V, Bahi-Buisson N, Wiame E, Hubert L, Boddaert N, Kaminska A, Habarou F, Desguerre I, Van Schaftingen E, Ottolenghi C, de Lonlay P.

Eur J Paediatr Neurol. 2016 Jan;20(1):53-60. doi: 10.1016/j.ejpn.2015.10.007. Epub 2015 Nov 5.

PubMed [citation]

PMID:: 26610677

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003260055.1

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

Description

This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 135 of the PHGDH protein (p.Arg135Gly). This variant is present in population databases (rs267606949, gnomAD 0.008%). This variant has not been reported in the literature in individuals affected with PHGDH-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant disrupts the p.Arg135T amino acid residue in PHGDH. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 19235232, 26610677). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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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