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NM_018082.6(POLR3B):c.1094C>T (p.Ala365Val) AND Charcot-Marie-Tooth disease, demyelinating, IIA 1I

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jun 17, 2022
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
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:
RCV001836975.2

Allele description [Variation Report for NM_018082.6(POLR3B):c.1094C>T (p.Ala365Val)]

NM_018082.6(POLR3B):c.1094C>T (p.Ala365Val)

Gene:
POLR3B:RNA polymerase III subunit B [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
12q23.3
Genomic location:
Preferred name:
NM_018082.6(POLR3B):c.1094C>T (p.Ala365Val)
HGVS:
  • NC_000012.12:g.106410953C>T
  • NG_031837.1:g.58296C>T
  • NM_001160708.2:c.920C>T
  • NM_018082.6:c.1094C>TMANE SELECT
  • NP_001154180.1:p.Ala307Val
  • NP_060552.4:p.Ala365Val
  • NC_000012.11:g.106804731C>T
  • NM_018082.5:c.1094C>T
Protein change:
A307V; ALA365VAL
Links:
OMIM: 614366.0011; dbSNP: rs2037218302
NCBI 1000 Genomes Browser:
rs2037218302
Molecular consequence:
  • NM_001160708.2:c.920C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_018082.6:c.1094C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Charcot-Marie-Tooth disease, demyelinating, IIA 1I
Synonyms:
CHARCOT-MARIE-TOOTH NEUROPATHY, TYPE 1I; Charcot-Marie-Tooth disease, demyelinating, type 1I
Identifiers:
MONDO: MONDO:0030677; MedGen: C5676914; OMIM: 619742

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002097580OMIM
no assertion criteria provided
Pathogenic
(Jun 17, 2022) 		germlineliterature only

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only

Citations

PubMed

De novo variants in POLR3B cause ataxia, spasticity, and demyelinating neuropathy.

Djordjevic D, Pinard M, Gauthier MS, Smith-Hicks C, Hoffman TL, Wolf NI, Oegema R, van Binsbergen E, Baskin B, Bernard G, Fribourg S, Coulombe B, Yoon G.

Am J Hum Genet. 2022 Apr 7;109(4):759-763. doi: 10.1016/j.ajhg.2022.03.006. No abstract available.

PubMed [citation]
PMID:
35395209
PMCID:
PMC9069058

Details of each submission

From OMIM, SCV002097580.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (1)

Description

In a 22-year-old man (patient 4) with demyelinating Charcot-Marie-Tooth disease type 1I (CMT1I; 619742), Djordjevic et al. (2021) identified a de novo heterozygous c.1094C-T transition (c.1094C-T, NM_018082.5) in the POLR3B gene, resulting in an ala365-to-val (A365V) substitution. The mutation was found by exome sequencing and confirmed by Sanger sequencing. Affinity purification coupled with mass spectrometry performed on HEK293 cells transfected with the variant showed that it impaired the association of POLR3B with other RNA pol III subunits. These findings suggested that the variant would render the enzyme inactive; the authors postulated a dominant-negative effect. In addition to a peripheral neuropathy, the patient had global developmental delay, progressive spasticity, and early-onset refractory epilepsy.

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

Last Updated: May 19, 2024