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NM_031448.6(C19orf12):c.326C>T (p.Ala109Val) AND Hereditary spastic paraplegia 43

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Mar 9, 2020
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:
RCV001305700.6

Allele description

NM_031448.6(C19orf12):c.326C>T (p.Ala109Val)

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.326C>T (p.Ala109Val)
HGVS:
  • NC_000019.10:g.29702812G>A
  • NG_031970.2:g.17978C>T
  • NM_001031726.4:c.326C>T
  • NM_001256046.3:c.291-20C>T
  • NM_001256047.2:c.326C>T
  • NM_001282929.1:c.134C>T
  • NM_001282930.3:c.134C>T
  • NM_001282931.3:c.134C>T
  • NM_031448.6:c.326C>TMANE SELECT
  • NP_001026896.3:p.Ala109Val
  • NP_001242976.1:p.Ala109Val
  • NP_001269858.1:p.Ala45Val
  • NP_001269859.1:p.Ala45Val
  • NP_001269860.1:p.Ala45Val
  • NP_113636.2:p.Ala109Val
  • NC_000019.9:g.30193719G>A
Protein change:
A109V
Links:
dbSNP: rs752858139
NCBI 1000 Genomes Browser:
rs752858139
Molecular consequence:
  • NM_001256046.3:c.291-20C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001031726.4:c.326C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001256047.2:c.326C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001282929.1:c.134C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001282930.3:c.134C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001282931.3:c.134C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_031448.6:c.326C>T - 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
SCV001495046Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Mar 9, 2020) 		germlineclinical testing

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

Help

Summary from all submissions

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

Citations

PubMed

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 Invitae, SCV001495046.4

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

Description

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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with C19orf12-related conditions. This variant is present in population databases (rs752858139, ExAC 0.02%). This sequence change replaces alanine with valine at codon 120 of the C19orf12 protein (p.Ala120Val). The alanine residue is weakly conserved and there is a small physicochemical difference between alanine and valine.

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

Last Updated: Mar 5, 2024