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NM_031448.6(C19orf12):c.163G>C (p.Gly55Arg) AND Hereditary spastic paraplegia 43

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
May 3, 2019
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:
RCV001060989.7

Allele description [Variation Report for NM_031448.6(C19orf12):c.163G>C (p.Gly55Arg)]

NM_031448.6(C19orf12):c.163G>C (p.Gly55Arg)

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.163G>C (p.Gly55Arg)
HGVS:
  • NC_000019.10:g.29702975C>G
  • NG_031970.2:g.17815G>C
  • NM_001031726.4:c.163G>C
  • NM_001256046.3:c.163G>C
  • NM_001256047.2:c.163G>C
  • NM_001282929.1:c.-30G>C
  • NM_001282930.3:c.-30G>C
  • NM_001282931.3:c.-30G>C
  • NM_031448.6:c.163G>CMANE SELECT
  • NP_001026896.2:p.Gly66Arg
  • NP_001026896.3:p.Gly55Arg
  • NP_001242975.1:p.Gly55Arg
  • NP_001242976.1:p.Gly55Arg
  • NP_113636.2:p.Gly55Arg
  • NC_000019.9:g.30193882C>G
  • NM_001031726.3:c.196G>C
Protein change:
G55R
Links:
dbSNP: rs1972192000
NCBI 1000 Genomes Browser:
rs1972192000
Molecular consequence:
  • NM_001282929.1:c.-30G>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001282930.3:c.-30G>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001282931.3:c.-30G>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001031726.4:c.163G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001256046.3:c.163G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001256047.2:c.163G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_031448.6:c.163G>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

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001225711Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(May 3, 2019) 		germlineclinical testing

PubMed (2)
[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

C19orf12 mutations in neurodegeneration with brain iron accumulation mimicking juvenile amyotrophic lateral sclerosis.

Deschauer M, Gaul C, Behrmann C, Prokisch H, Zierz S, Haack TB.

J Neurol. 2012 Nov;259(11):2434-9. doi: 10.1007/s00415-012-6521-7. Epub 2012 May 15.

PubMed [citation]
PMID:
22584950

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 Labcorp Genetics (formerly Invitae), Labcorp, SCV001225711.5

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

Description

This sequence change replaces glycine with arginine at codon 66 of the C19orf12 protein (p.Gly66Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. 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. This variant disrupts the p.Gly66 amino acid residue in C19orf12. Other variant(s) that disrupt this residue have been observed in individuals with C19orf12-related conditions (PMID: 22584950), suggesting that it is a clinically significant residue. As a result, variants that disrupt this residue are likely to be causative of disease. 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: "Possibly Damaging"; Align-GVGD: "Class C15"). This variant has not been reported in the literature in individuals with C19orf12-related conditions. This variant is not present in population databases (ExAC no frequency).

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

Last Updated: Sep 29, 2024