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NM_031448.6(C19orf12):c.161G>C (p.Gly54Ala) AND Hereditary spastic paraplegia 43

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:
RCV002241377.4

Allele description [Variation Report for NM_031448.6(C19orf12):c.161G>C (p.Gly54Ala)]

NM_031448.6(C19orf12):c.161G>C (p.Gly54Ala)

Gene:
C19orf12:chromosome 19 open reading frame 12 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
19q12
Genomic location:
Preferred name:
NM_031448.6(C19orf12):c.161G>C (p.Gly54Ala)
HGVS:
  • NC_000019.10:g.29702977C>G
  • NG_031970.2:g.17813G>C
  • NM_001031726.4:c.161G>C
  • NM_001256046.3:c.161G>C
  • NM_001256047.2:c.161G>C
  • NM_001282929.1:c.-32G>C
  • NM_001282930.3:c.-32G>C
  • NM_001282931.3:c.-32G>C
  • NM_031448.6:c.161G>CMANE SELECT
  • NP_001026896.3:p.Gly54Ala
  • NP_001242975.1:p.Gly54Ala
  • NP_001242976.1:p.Gly54Ala
  • NP_113636.2:p.Gly54Ala
  • NC_000019.9:g.30193884C>G
  • NM_001031726.3:c.194G>C
Protein change:
G54A
Links:
dbSNP: rs752450983
NCBI 1000 Genomes Browser:
rs752450983
Molecular consequence:
  • NM_001282929.1:c.-32G>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001282930.3:c.-32G>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001282931.3:c.-32G>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001031726.4:c.161G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001256046.3:c.161G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001256047.2:c.161G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_031448.6:c.161G>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Hereditary spastic paraplegia 43
Synonyms:
Spastic paraplegia 43, autosomal recessive
Identifiers:
MONDO: MONDO:0014024; MedGen: C2680446; Orphanet: 320370; OMIM: 615043

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002510914Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Oct 13, 2023) 		germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

Help

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 (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002510914.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

This sequence change replaces glycine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 65 of the C19orf12 protein (p.Gly65Ala). This variant is present in population databases (rs752450983, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with C19orf12-related conditions. ClinVar contains an entry for this variant (Variation ID: 1195848). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. This variant disrupts the p.Gly65 amino acid residue in C19orf12. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 21981780, 23269600, 31087512). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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.

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

Last Updated: Sep 29, 2024