NM_000533.5(PLP1):c.173A>G (p.Tyr58Cys) AND Pelizaeus-Merzbacher disease

Germline classification:: Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:: Apr 4, 2019
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:: RCV001196160.4

Allele description [Variation Report for NM_000533.5(PLP1):c.173A>G (p.Tyr58Cys)]

NM_000533.5(PLP1):c.173A>G (p.Tyr58Cys)

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.173A>G (p.Tyr58Cys)

HGVS:

NC_000023.11:g.103785750A>G
NG_008863.2:g.14240A>G
NG_016452.2:g.51533T>C
NM_000533.5:c.173A>GMANE SELECT
NM_001128834.3:c.173A>G
NM_001305004.1:c.8A>G
NM_199478.3:c.173A>G
NP_000524.3:p.Tyr58Cys
NP_001122306.1:p.Tyr58Cys
NP_001291933.1:p.Tyr3Cys
NP_955772.1:p.Tyr58Cys
NC_000023.10:g.103040679A>G
NM_000533.3:c.173A>G

Protein change:

Y3C

Links:

dbSNP: rs2074490307

NCBI 1000 Genomes Browser:

rs2074490307

Molecular consequence:

NM_000533.5:c.173A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001128834.3:c.173A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001305004.1:c.8A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_199478.3:c.173A>G - 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

Recent activity

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methyl-CpG-binding domain protein 1 isoform 5 [Homo sapiens]
methyl-CpG-binding domain protein 1 isoform 5 [Homo sapiens]
gi|21464119|ref|NP_056723.2|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001366681	Centre for Mendelian Genomics, University Medical Centre Ljubljana	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Apr 4, 2019)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV005077957	Molecular Diagnostics Lab, Nemours Children's Health, Delaware	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic	unknown	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

SCV001366681

Centre for Mendelian Genomics, University Medical Centre Ljubljana

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Apr 4, 2019)

unknown

clinical testing

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

SCV005077957

Molecular Diagnostics Lab, Nemours Children's Health, Delaware

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic

unknown

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	unknown	yes	1	not provided	not provided	1	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 Centre for Mendelian Genomics, University Medical Centre Ljubljana, SCV001366681.2

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

Description

This variant was classified as: Pathogenic. The following ACMG criteria were applied in classifying this variant: PM2,PS1,PS3,PP3. This variant was detected in hemizygous state.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Molecular Diagnostics Lab, Nemours Children's Health, Delaware, SCV005077957.2

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

Description

This missense variant (c.173A>G, p.Tyr58Cys) has not been reported in population databases (gnomAD) and has not been described in the literature. Variant prediction programs suggest a deleterious effect but no functional studies have been published.

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

Last Updated: Aug 18, 2024

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