U.S. flag

An official website of the United States government

NM_031448.6(C19orf12):c.332T>C (p.Val111Ala) AND Neurodegeneration with brain iron accumulation 4

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Apr 4, 2021
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:
RCV001644555.1

Allele description [Variation Report for NM_031448.6(C19orf12):c.332T>C (p.Val111Ala)]

NM_031448.6(C19orf12):c.332T>C (p.Val111Ala)

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.332T>C (p.Val111Ala)
Other names:
p.Val122Ala
HGVS:
  • NC_000019.10:g.29702806A>G
  • NG_031970.2:g.17984T>C
  • NM_001031726.4:c.332T>C
  • NM_001256046.3:c.291-14T>C
  • NM_001256047.2:c.332T>C
  • NM_001282929.1:c.140T>C
  • NM_001282930.3:c.140T>C
  • NM_001282931.3:c.140T>C
  • NM_031448.6:c.332T>CMANE SELECT
  • NP_001026896.3:p.Val111Ala
  • NP_001242976.1:p.Val111Ala
  • NP_001269858.1:p.Val47Ala
  • NP_001269859.1:p.Val47Ala
  • NP_001269860.1:p.Val47Ala
  • NP_113636.2:p.Val111Ala
  • NC_000019.9:g.30193713A>G
  • NM_001031726.3:c.365T>C
Protein change:
V111A
Links:
dbSNP: rs1972173461
NCBI 1000 Genomes Browser:
rs1972173461
Molecular consequence:
  • NM_001256046.3:c.291-14T>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001031726.4:c.332T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001256047.2:c.332T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001282929.1:c.140T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001282930.3:c.140T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001282931.3:c.140T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_031448.6:c.332T>C - missense variant - [Sequence Ontology: SO:0001583]
Functional consequence:
Unknown function
Observations:
1

Condition(s)

Name:
Neurodegeneration with brain iron accumulation 4 (NBIA4)
Synonyms:
MITOCHONDRIAL PROTEIN-ASSOCIATED NEURODEGENERATION
Identifiers:
MONDO: MONDO:0013674; MedGen: C3280371; Orphanet: 289560; OMIM: 614298

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001852736Foundation for Research in Genetics and Endocrinology, FRIGE's Institute of Human Genetics
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain significance
(Apr 4, 2021) 		germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
Indiangermlineyes1not providednot providednot providednot providedclinical testing

Citations

PubMed

A new phenotype of brain iron accumulation with dystonia, optic atrophy, and peripheral neuropathy.

Horvath R, Holinski-Feder E, Neeve VC, Pyle A, Griffin H, Ashok D, Foley C, Hudson G, Rautenstrauss B, Nürnberg G, Nürnberg P, Kortler J, Neitzel B, Bässmann I, Rahman T, Keavney B, Loughlin J, Hambleton S, Schoser B, Lochmüller H, Santibanez-Koref M, Chinnery PF.

Mov Disord. 2012 May;27(6):789-93. doi: 10.1002/mds.24980. Epub 2012 Apr 16.

PubMed [citation]
PMID:
22508347

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From Foundation for Research in Genetics and Endocrinology, FRIGE's Institute of Human Genetics, SCV001852736.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1Indian1not providednot providedclinical testing PubMed (2)

Description

A homozygous missense variation in exon 3 of the C19orf12 gene that results in the amino acid substitution of Alanine for Valine at codon 122 was detected. The observed variant c.365T>C (p.Val122Ala) has a minor allele frequency of 0.001% in the 1000 genomes and gnomAD databases. A different missense variant affecting nearby codon *Leu121Gln) has previously been reported in patients affected with neurodegeneration with brain iron accumulation (Hovarth et al 2012). The in silico prediction of the variant are probably by PolyPhen-2 (HumDiv) and damaging by SIFT, LRT and MutationTaster2. The reference codon is conserved across species. In summary, the variant meets our criteria to be classified as a variant of uncertain significance.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot provided1not providednot providednot provided

Last Updated: Dec 24, 2023