NM_006623.4(PHGDH):c.357-1G>A AND Neu-Laxova syndrome 1

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:: RCV001420191.4

Allele description [Variation Report for NM_006623.4(PHGDH):c.357-1G>A]

NM_006623.4(PHGDH):c.357-1G>A

Gene:

PHGDH:phosphoglycerate dehydrogenase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1p12

Genomic location:

Preferred name:

NM_006623.4(PHGDH):c.357-1G>A

HGVS:

NC_000001.11:g.119726850G>A
NG_009188.1:g.20055G>A
NM_006623.4:c.357-1G>AMANE SELECT
NC_000001.10:g.120269473G>A

Links:

dbSNP: rs766427173

NCBI 1000 Genomes Browser:

rs766427173

Molecular consequence:

NM_006623.4:c.357-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]

Functional consequence:

Decreased function
effect on RNA splicing [Variation Ontology: 0362]

Observations:

Condition(s)

Name:: Neu-Laxova syndrome 1 (NLS1)
Identifiers:: MONDO: MONDO:0009736; MedGen: C4551478; Orphanet: 2671; OMIM: 256520

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001622388	Foundation for Research in Genetics and Endocrinology, FRIGE's Institute of Human Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Dec 7, 2020)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002549053	Diagnostics Division, CENTRE FOR DNA FINGERPRINTING AND DIAGNOSTICS	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic	germline	research	PubMed (1) [See all records that cite this PMID]
SCV004049058	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

SCV001622388

Foundation for Research in Genetics and Endocrinology, FRIGE's Institute of Human Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Dec 7, 2020)

germline

clinical testing

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

SCV002549053

Diagnostics Division, CENTRE FOR DNA FINGERPRINTING AND DIAGNOSTICS

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic

germline

research

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

SCV004049058

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	yes	1	not provided	not provided	not provided	not provided	research
not provided	germline	no	not provided	not provided	not provided	not provided	not provided	clinical testing
Hindu	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Foundation for Research in Genetics and Endocrinology, FRIGE's Institute of Human Genetics, SCV001622388.1

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

Description

A heterozygous 3â€™splice site variation in intron 3 of the PHGDH gene that affects the invariant AG acceptor splice site upstream of exon 4 was detected. The observed variant c.3357-1G>A has not been reported in the 1000 genomes and has a minor allele frequency of 0.008% in the gnomAD databases. The in silico prediction of the variant is damaging by MutationTaster2. The reference codon is conserved across species. In summary, the variant meets our criteria to be classified as pathogenic.

#	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		1	not provided	not provided	not provided

From Diagnostics Division, CENTRE FOR DNA FINGERPRINTING AND DIAGNOSTICS, SCV002549053.1

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

#	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		1	not provided	not provided	not provided

From Genome-Nilou Lab, SCV004049058.1

#	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: Jun 23, 2024

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