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NM_001352514.2(HLCS):c.1156C>T (p.Gln386Ter) AND Holocarboxylase synthetase deficiency

Germline classification:
Pathogenic (1 submission)
Last evaluated:
May 8, 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:
RCV001388680.4

Allele description [Variation Report for NM_001352514.2(HLCS):c.1156C>T (p.Gln386Ter)]

NM_001352514.2(HLCS):c.1156C>T (p.Gln386Ter)

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.1156C>T (p.Gln386Ter)
HGVS:
  • NC_000021.9:g.36936730G>A
  • NG_016193.2:g.58665C>T
  • NM_000411.8:c.715C>T
  • NM_001242784.3:c.715C>T
  • NM_001242785.2:c.715C>T
  • NM_001352514.2:c.1156C>TMANE SELECT
  • NM_001352515.2:c.715C>T
  • NM_001352516.2:c.715C>T
  • NM_001352517.1:c.715C>T
  • NM_001352518.2:c.715C>T
  • NP_000402.3:p.Gln239Ter
  • NP_001229713.1:p.Gln239Ter
  • NP_001229714.1:p.Gln239Ter
  • NP_001339443.1:p.Gln386Ter
  • NP_001339444.1:p.Gln239Ter
  • NP_001339445.1:p.Gln239Ter
  • NP_001339446.1:p.Gln239Ter
  • NP_001339447.1:p.Gln239Ter
  • NC_000021.8:g.38309030G>A
  • NR_148020.2:n.1015C>T
  • NR_148021.1:n.1172C>T
Protein change:
Q239*
Links:
dbSNP: rs2146525207
NCBI 1000 Genomes Browser:
rs2146525207
Molecular consequence:
  • NR_148020.2:n.1015C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_148021.1:n.1172C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NM_000411.8:c.715C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001242784.3:c.715C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001242785.2:c.715C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001352514.2:c.1156C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001352515.2:c.715C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001352516.2:c.715C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001352517.1:c.715C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001352518.2:c.715C>T - nonsense - [Sequence Ontology: SO:0001587]

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

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001589754Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(May 8, 2020) 		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

Mutations in the holocarboxylase synthetase gene HLCS.

Suzuki Y, Yang X, Aoki Y, Kure S, Matsubara Y.

Hum Mutat. 2005 Oct;26(4):285-90. Review.

PubMed [citation]
PMID:
16134170

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, SCV001589754.4

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

Description

This sequence change creates a premature translational stop signal (p.Gln239*) in the HLCS gene. It is expected to result in an absent or disrupted protein product. For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in HLCS are known to be pathogenic (PMID: 16134170). This variant has not been reported in the literature in individuals with HLCS-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: Feb 28, 2024