NM_001031726.3(C19orf12):c.205G>A (p.Gly69Arg) AND Spastic paraplegia 43, autosomal recessive

Clinical significance:Pathogenic (Last evaluated: Feb 20, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000528859.4

Allele description [Variation Report for NM_001031726.3(C19orf12):c.205G>A (p.Gly69Arg)]

NM_001031726.3(C19orf12):c.205G>A (p.Gly69Arg)

Gene:
C19orf12:chromosome 19 open reading frame 12 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
19q12
Genomic location:
Preferred name:
NM_001031726.3(C19orf12):c.205G>A (p.Gly69Arg)
Other names:
C19ORF12, GLY69ARG
HGVS:
  • NC_000019.10:g.29702966C>T
  • NG_031970.1:g.17824G>A
  • NG_031970.2:g.17824G>A
  • NM_001031726.3:c.205G>A
  • NM_001256046.2:c.172G>A
  • NM_001256047.1:c.172G>A
  • NM_001282929.1:c.-21G>A
  • NM_001282930.2:c.-21G>A
  • NM_001282931.2:c.-21G>A
  • NM_031448.5:c.172G>A
  • NP_001026896.2:p.Gly69Arg
  • NP_001026896.2:p.Gly69Arg
  • NP_001242975.1:p.Gly58Arg
  • NP_001242976.1:p.Gly58Arg
  • NP_113636.2:p.Gly58Arg
  • NC_000019.9:g.30193873C>T
  • NM_001031726.2:c.205G>A
  • Q9NSK7:p.Gly69Arg
Note:
ClinGen staff contributed the HGVS expression for this variant.
Protein change:
G58R; GLY69ARG
Links:
UniProtKB: Q9NSK7#VAR_066620; OMIM: 614297.0003; dbSNP: rs515726205
NCBI 1000 Genomes Browser:
rs515726205
Molecular consequence:
  • NM_001282929.1:c.-21G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001282930.2:c.-21G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001282931.2:c.-21G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001031726.3:c.205G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001256046.2:c.172G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001256047.1:c.172G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_031448.5:c.172G>A - missense variant - [Sequence Ontology: SO:0001583]
Functional consequence:
Unknown function

Condition(s)

Name:
Spastic paraplegia 43, autosomal recessive (SPG43)
Identifiers:
MONDO: MONDO:0014024; MedGen: C2680446; Orphanet: 320370; OMIM: 615043

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000647089Invitaecriteria provided, single submitter
Pathogenic
(Feb 20, 2020)
germlineclinical testing

PubMed (7)
[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

Absence of an orphan mitochondrial protein, c19orf12, causes a distinct clinical subtype of neurodegeneration with brain iron accumulation.

Hartig MB, Iuso A, Haack T, Kmiec T, Jurkiewicz E, Heim K, Roeber S, Tarabin V, Dusi S, Krajewska-Walasek M, Jozwiak S, Hempel M, Winkelmann J, Elstner M, Oexle K, Klopstock T, Mueller-Felber W, Gasser T, Trenkwalder C, Tiranti V, Kretzschmar H, Schmitz G, et al.

Am J Hum Genet. 2011 Oct 7;89(4):543-50. doi: 10.1016/j.ajhg.2011.09.007.

PubMed [citation]
PMID:
21981780
PMCID:
PMC3188837

New NBIA subtype: genetic, clinical, pathologic, and radiographic features of MPAN.

Hogarth P, Gregory A, Kruer MC, Sanford L, Wagoner W, Natowicz MR, Egel RT, Subramony SH, Goldman JG, Berry-Kravis E, Foulds NC, Hammans SR, Desguerre I, Rodriguez D, Wilson C, Diedrich A, Green S, Tran H, Reese L, Woltjer RL, Hayflick SJ.

Neurology. 2013 Jan 15;80(3):268-75. doi: 10.1212/WNL.0b013e31827e07be. Epub 2012 Dec 26.

PubMed [citation]
PMID:
23269600
PMCID:
PMC3589182
See all PubMed Citations (7)

Details of each submission

From Invitae, SCV000647089.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (7)

Description

This sequence change replaces glycine with arginine at codon 69 of the C19orf12 protein (p.Gly69Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is present in population databases (rs515726205, ExAC 0.005%). This variant has been observed to be homozygous or in combination with another C19orf12 variant in several individuals affected with neurodegeneration with brain iron accumulation (NBIA) (PMID: 21981780, 23269600, 23494994, 25592411, 30088953). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 31157). Experimental evidence suggests that this variant results in altered protein localization compared to wild-type protein (PMID: 23857908). For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: May 23, 2021

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