NM_000304.4(PMP22):c.458A>G (p.Tyr153Cys) AND Charcot-Marie-Tooth disease, type I

This record was updated by the submitter. Please see the current version.

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Oct 13, 2023
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:: RCV001911471.5

Allele description

NM_000304.4(PMP22):c.458A>G (p.Tyr153Cys)

Gene:

PMP22:peripheral myelin protein 22 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

17p12

Genomic location:

Preferred name:

NM_000304.4(PMP22):c.458A>G (p.Tyr153Cys)

HGVS:

NC_000017.11:g.15230942T>C
NG_007949.1:g.39386A>G
NM_000304.4:c.458A>GMANE SELECT
NM_001281455.2:c.458A>G
NM_001281456.2:c.458A>G
NM_153321.3:c.458A>G
NM_153322.3:c.458A>G
NP_000295.1:p.Tyr153Cys
NP_001268384.1:p.Tyr153Cys
NP_001268385.1:p.Tyr153Cys
NP_696996.1:p.Tyr153Cys
NP_696997.1:p.Tyr153Cys
LRG_263t1:c.458A>G
LRG_263:g.39386A>G
NC_000017.10:g.15134259T>C
NM_000304.2:c.458A>G
NR_104017.2:n.553A>G
NR_104018.2:n.453A>G

Protein change:

Y153C

Links:

dbSNP: rs761138676

NCBI 1000 Genomes Browser:

rs761138676

Molecular consequence:

NM_000304.4:c.458A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001281455.2:c.458A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001281456.2:c.458A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_153321.3:c.458A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_153322.3:c.458A>G - missense variant - [Sequence Ontology: SO:0001583]
NR_104017.2:n.553A>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_104018.2:n.453A>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Charcot-Marie-Tooth disease, type I (CMT1)
Synonyms:: Charcot-Marie-Tooth Neuropathy Type 1; Hereditary Motor and Sensory Neuropathy 1; Charcot-Marie-Tooth, Type 1
Identifiers:: MONDO: MONDO:0019011; MedGen: C0751036

Recent activity

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hypothetical protein [Adlercreutzia equolifaciens]
hypothetical protein [Adlercreutzia equolifaciens]
gi|550993981|ref|WP_022738769.1|

Protein
Mus musculus predicted gene, 20362 (Gm20362), transcript variant 1, long non-cod...
Mus musculus predicted gene, 20362 (Gm20362), transcript variant 1, long non-coding RNA
gi|339515641|ref|NR_040301.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002172501	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Oct 13, 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

SCV002172501

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Oct 13, 2023)

germline

clinical testing

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

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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

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

Details of each submission

From Invitae, SCV002172501.3

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

Description

This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 153 of the PMP22 protein (p.Tyr153Cys). This variant is present in population databases (rs761138676, gnomAD 0.0009%). This missense change has been observed in individual(s) with clinical features of PMP22-related conditions (Invitae). ClinVar contains an entry for this variant (Variation ID: 1400754). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt PMP22 protein function. 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: May 1, 2024

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