NM_006623.4(PHGDH):c.1394del (p.Leu465fs) AND PHGDH deficiency

Germline classification:: Pathogenic/Likely pathogenic (3 submissions)
Last evaluated:: Apr 11, 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:: RCV003012523.6

Allele description [Variation Report for NM_006623.4(PHGDH):c.1394del (p.Leu465fs)]

NM_006623.4(PHGDH):c.1394del (p.Leu465fs)

Gene:

PHGDH:phosphoglycerate dehydrogenase [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

1p12

Genomic location:

Preferred name:

NM_006623.4(PHGDH):c.1394del (p.Leu465fs)

HGVS:

NC_000001.11:g.119742991del
NG_009188.1:g.36196del
NM_006623.3:c.1394delT
NM_006623.4:c.1394delMANE SELECT
NP_006614.2:p.Leu465fs
NC_000001.10:g.120285614del
NM_006623.4:c.1394del

Protein change:

L465fs

Links:

dbSNP: rs2464204681

NCBI 1000 Genomes Browser:

rs2464204681

Molecular consequence:

NM_006623.4:c.1394del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003314559	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Aug 21, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 30348640, 28492532
SCV003844371	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Likely pathogenic (Feb 1, 2023)	germline	clinical testing	Citation Link,
SCV004049133	Genome-Nilou Lab	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Apr 11, 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

SCV003314559

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Aug 21, 2022)

germline

clinical testing

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

SCV003844371

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Likely pathogenic
(Feb 1, 2023)

germline

clinical testing

Citation Link,

SCV004049133

Genome-Nilou Lab

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Apr 11, 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
not provided	germline	no	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Reduction of stratum corneum ceramides in Neu-Laxova syndrome caused by phosphoglycerate dehydrogenase deficiency.

Takeichi T, Okuno Y, Kawamoto A, Inoue T, Nagamoto E, Murase C, Shimizu E, Tanaka K, Kageshita Y, Fukushima S, Kono M, Ishikawa J, Ihn H, Takahashi Y, Akiyama M.

J Lipid Res. 2018 Dec;59(12):2413-2420. doi: 10.1194/jlr.P087536. Epub 2018 Oct 22.

PubMed [citation]

PMID:: 30348640
PMCID:: PMC6277160

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 Labcorp Genetics (formerly Invitae), Labcorp, SCV003314559.3

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

Description

This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Leu465Argfs*17) in the PHGDH gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 69 amino acid(s) of the PHGDH protein. For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the PHGDH protein in which other variant(s) (p.Trp506*) have been determined to be pathogenic (PMID: 30348640; Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. This variant has not been reported in the literature in individuals affected with PHGDH-related conditions.

#	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 Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV003844371.1

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

Description

Variant summary: PHGDH c.1394delT (p.Leu465ArgfsX17) results in a premature termination codon and is predicted to cause a truncation of the encoded protein, which is a commonly known mechanism for disease. Although the variant is not predicted to cause absence of the protein through nonsense mediated decay, the variant is predicted to disrupt the last 52 amino acids in the protein sequence. Downstream missense variants have been classified as pathogenic by our lab, suggesting that the disrupted region is important for normal protein function (e.g. c.1468G>A [p.Val490Met]). The variant was absent in 251444 control chromosomes (gnomAD). To our knowledge, no occurrence of c.1394delT in individuals affected with Phosphoglycerate Dehydrogenase Deficiency and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic.

#	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 Genome-Nilou Lab, SCV004049133.1

#	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	germline	no	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: May 16, 2025

ClinVar

Relating variation to medicine