NM_000533.5(PLP1):c.94T>C (p.Phe32Leu) AND Pelizaeus-Merzbacher disease

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Feb 25, 2022
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:: RCV004595809.1

Allele description [Variation Report for NM_000533.5(PLP1):c.94T>C (p.Phe32Leu)]

NM_000533.5(PLP1):c.94T>C (p.Phe32Leu)

Genes:

RAB9B:RAB9B, member RAS oncogene family [Gene - OMIM - HGNC]
PLP1:proteolipid protein 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

Xq22.2

Genomic location:

Preferred name:

NM_000533.5(PLP1):c.94T>C (p.Phe32Leu)

HGVS:

NC_000023.11:g.103785671T>C
NG_008863.2:g.14161T>C
NG_016452.2:g.51612A>G
NM_000533.5:c.94T>CMANE SELECT
NM_001128834.3:c.94T>C
NM_001305004.1:c.5-76T>C
NM_199478.3:c.94T>C
NP_000524.3:p.Phe32Leu
NP_001122306.1:p.Phe32Leu
NP_955772.1:p.Phe32Leu
NC_000023.10:g.103040600T>C

Protein change:

F32L

Molecular consequence:

NM_001305004.1:c.5-76T>C - intron variant - [Sequence Ontology: SO:0001627]
NM_000533.5:c.94T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001128834.3:c.94T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_199478.3:c.94T>C - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Name:: Pelizaeus-Merzbacher disease
Synonyms:: LEUKODYSTROPHY, HYPOMYELINATING, 1; Pelizaeus Merzbacher brain sclerosis; Sudanophilic leukodystrophy; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0010714; MedGen: C0205711; Orphanet: 702; OMIM: 312080; Human Phenotype Ontology: HP:0003269

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV005088512	Molecular Diagnostics Lab, Nemours Children's Health, Delaware	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Feb 25, 2022)	unknown	clinical testing	PubMed (4) [See all records that cite these PMIDs] 11093273, 29451896, 9106132, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV005088512

Molecular Diagnostics Lab, Nemours Children's Health, Delaware

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Feb 25, 2022)

unknown

clinical testing

PubMed (4)
[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	unknown	yes	2	not provided	not provided	2	not provided	clinical testing

Citations

PubMed

Genotype-phenotype correlation in inherited brain myelination defects due to proteolipid protein gene mutations. Clinical European Network on Brain Dysmyelinating Disease.

Cailloux F, Gauthier-Barichard F, Mimault C, Isabelle V, Courtois V, Giraud G, Dastugue B, Boespflug-Tanguy O.

Eur J Hum Genet. 2000 Nov;8(11):837-45.

PubMed [citation]

PMID:: 11093273

Hypomyelinating disorders in China: The clinical and genetic heterogeneity in 119 patients.

Ji H, Li D, Wu Y, Zhang Q, Gu Q, Xie H, Ji T, Wang H, Zhao L, Zhao H, Yang Y, Feng H, Xiong H, Ji J, Yang Z, Kou L, Li M, Bao X, Chang X, Zhang Y, Li L, Li H, et al.

PLoS One. 2018;13(2):e0188869. doi: 10.1371/journal.pone.0188869.

PubMed [citation]

PMID:: 29451896
PMCID:: PMC5815574

See all PubMed Citations (4)

Details of each submission

From Molecular Diagnostics Lab, Nemours Children's Health, Delaware, SCV005088512.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing (GTR000028364.3)	PubMed (4)
2	not provided	1	not provided	not provided	clinical testing (GTR000028364.3)	PubMed (4)

Description

This missense variant (c.94T>C, p.Phe32Leu) has not been observed in population databases (gnomAD). It has been described in the literature (PMID 11093273, PMID 39451896, PMID 9106132). Variant prediction programs support a deleterious effect on the protein, but functional studies have not been reported.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	yes	1	blood	not provided	(GTR000028364.3)	1	not provided	not provided	not provided
2	unknown	yes	1	blood	not provided	(GTR000028364.3)	1	not provided	not provided	not provided

Last Updated: Jul 29, 2024

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