NM_181882.3(PRX):c.2245A>G (p.Lys749Glu) AND Charcot-Marie-Tooth disease type 4

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

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 5, 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:: RCV001969725.5

Allele description

NM_181882.3(PRX):c.2245A>G (p.Lys749Glu)

Gene:

PRX:periaxin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

19q13.2

Genomic location:

Preferred name:

NM_181882.3(PRX):c.2245A>G (p.Lys749Glu)

HGVS:

NC_000019.10:g.40396107T>C
NG_007979.1:g.22258A>G
NM_020956.2:c.*2450A>G
NM_181882.3:c.2245A>GMANE SELECT
NP_870998.2:p.Lys749Glu
LRG_265t1:c.*2450A>G
LRG_265:g.22258A>G
NC_000019.9:g.40902014T>C

Protein change:

K749E

Links:

dbSNP: rs755014286

NCBI 1000 Genomes Browser:

rs755014286

Molecular consequence:

NM_020956.2:c.*2450A>G - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_181882.3:c.2245A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Charcot-Marie-Tooth disease type 4
Synonyms:: Charcot-Marie-Tooth, Type 4
Identifiers:: MONDO: MONDO:0018995; MedGen: C4082197

Recent activity

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RNA polymerase sigma factor, sigma-54 family [Chlamydia pneumoniae AR39]
RNA polymerase sigma factor, sigma-54 family [Chlamydia pneumoniae AR39]
gi|8163554|gb|AAF73732.1||gnl|TIGR| 1

Protein
del(6q21)
del(6q21)

MedGen
Deletion 1p36
Deletion 1p36

MedGen
del(17p13)
del(17p13)

MedGen
del(10q24q25)
del(10q24q25)

MedGen

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002224850	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jul 5, 2022)	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

SCV002224850

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jul 5, 2022)

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

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, SCV002224850.3

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

Description

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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 1441853). This variant has not been reported in the literature in individuals affected with PRX-related conditions. This variant is present in population databases (rs755014286, gnomAD 0.005%). This sequence change replaces lysine, which is basic and polar, with glutamic acid, which is acidic and polar, at codon 749 of the PRX protein (p.Lys749Glu).

#	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: Feb 14, 2024

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