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NM_001352514.2(HLCS):c.989G>C (p.Arg330Pro) AND Holocarboxylase synthetase deficiency

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Jan 22, 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:
RCV001067305.8

Allele description [Variation Report for NM_001352514.2(HLCS):c.989G>C (p.Arg330Pro)]

NM_001352514.2(HLCS):c.989G>C (p.Arg330Pro)

Gene:
HLCS:holocarboxylase synthetase [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
21q22.13
Genomic location:
Preferred name:
NM_001352514.2(HLCS):c.989G>C (p.Arg330Pro)
HGVS:
  • NC_000021.9:g.36936897C>G
  • NG_016193.2:g.58498G>C
  • NM_000411.8:c.548G>C
  • NM_001242784.3:c.548G>C
  • NM_001242785.2:c.548G>C
  • NM_001352514.2:c.989G>CMANE SELECT
  • NM_001352515.2:c.548G>C
  • NM_001352516.2:c.548G>C
  • NM_001352517.1:c.548G>C
  • NM_001352518.2:c.548G>C
  • NP_000402.3:p.Arg183Pro
  • NP_001229713.1:p.Arg183Pro
  • NP_001229714.1:p.Arg183Pro
  • NP_001339443.1:p.Arg330Pro
  • NP_001339444.1:p.Arg183Pro
  • NP_001339445.1:p.Arg183Pro
  • NP_001339446.1:p.Arg183Pro
  • NP_001339447.1:p.Arg183Pro
  • NC_000021.8:g.38309197C>G
  • NM_000411.6:c.548G>C
  • NR_148020.2:n.848G>C
  • NR_148021.1:n.1005G>C
Protein change:
R183P
Links:
dbSNP: rs368754318
NCBI 1000 Genomes Browser:
rs368754318
Molecular consequence:
  • NM_000411.8:c.548G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001242784.3:c.548G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001242785.2:c.548G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001352514.2:c.989G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001352515.2:c.548G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001352516.2:c.548G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001352517.1:c.548G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001352518.2:c.548G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NR_148020.2:n.848G>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_148021.1:n.1005G>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:
Holocarboxylase synthetase deficiency
Synonyms:
MULTIPLE CARBOXYLASE DEFICIENCY, EARLY ONSET
Identifiers:
MONDO: MONDO:0009666; MedGen: C0268581; Orphanet: 79242; OMIM: 253270

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001232359Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Uncertain significance
(Jan 22, 2020)
germlineclinical testing

PubMed (2)
[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

Relationship between kinetic properties of mutant enzyme and biochemical and clinical responsiveness to biotin in holocarboxylase synthetase deficiency.

Sakamoto O, Suzuki Y, Li X, Aoki Y, Hiratsuka M, Suormala T, Baumgartner ER, Gibson KM, Narisawa K.

Pediatr Res. 1999 Dec;46(6):671-6.

PubMed [citation]
PMID:
10590022

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, SCV001232359.5

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

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. This variant has been reported to affect HLCS protein function (PMID: 10590022). This variant has been observed in an individual with holocarboxylase synthetase deficiency (PMID: 10590022). This variant is not present in population databases (ExAC no frequency). This sequence change replaces arginine with proline at codon 183 of the HLCS protein (p.Arg183Pro). The arginine residue is moderately conserved and there is a moderate physicochemical difference between arginine and proline.

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

Last Updated: Sep 29, 2024