NM_021629.4(GNB4):c.169A>G (p.Lys57Glu) AND Charcot-Marie-Tooth disease, dominant intermediate F

Clinical significance:Likely pathogenic (Last evaluated: Mar 23, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001061902.2

Allele description [Variation Report for NM_021629.4(GNB4):c.169A>G (p.Lys57Glu)]

NM_021629.4(GNB4):c.169A>G (p.Lys57Glu)

Gene:
GNB4:G protein subunit beta 4 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
3q26.33
Genomic location:
Preferred name:
NM_021629.4(GNB4):c.169A>G (p.Lys57Glu)
HGVS:
  • NC_000003.12:g.179419433T>C
  • NG_033163.1:g.37151A>G
  • NM_021629.4:c.169A>GMANE SELECT
  • NP_067642.1:p.Lys57Glu
  • NC_000003.11:g.179137221T>C
  • NM_021629.3:c.169A>G
Protein change:
K57E
Links:
dbSNP: rs1714910248
NCBI 1000 Genomes Browser:
rs1714910248
Molecular consequence:
  • NM_021629.4:c.169A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Charcot-Marie-Tooth disease, dominant intermediate F (CMTDIF)
Identifiers:
MONDO: MONDO:0014074; MedGen: C3554654; Orphanet: 352670; OMIM: 615185

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001226665Invitaecriteria provided, single submitter
Likely pathogenic
(Mar 23, 2020)
germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Confirmation of the GNB4 gene as causal for Charcot-Marie-Tooth disease by a novel de novo mutation in a Czech patient.

Laššuthová P, Šafka Brožková D, Neupauerová J, Krůtová M, Mazanec R, Seeman P.

Neuromuscul Disord. 2017 Jan;27(1):57-60. doi: 10.1016/j.nmd.2016.09.010. Epub 2016 Sep 22.

PubMed [citation]
PMID:
27908631

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):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV001226665.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

This sequence change replaces lysine with glutamic acid at codon 57 of the GNB4 protein (p.Lys57Glu). The lysine residue is highly conserved and there is a small physicochemical difference between lysine and glutamic acid. This variant is not present in population databases (ExAC no frequency). This variant has been observed to be de novo in an individual affected with Charcot-Marie-Tooth disease (PMID: 27908631). 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: Deleterious; PolyPhen-2: Benign; Align-GVGD: Class C0). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Nov 27, 2021

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