NM_001352514.2(HLCS):c.691G>T (p.Glu231Ter) AND Holocarboxylase synthetase deficiency

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Apr 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:: RCV000702080.3

Allele description [Variation Report for NM_001352514.2(HLCS):c.691G>T (p.Glu231Ter)]

NM_001352514.2(HLCS):c.691G>T (p.Glu231Ter)

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.691G>T (p.Glu231Ter)

HGVS:

NC_000021.9:g.36937195C>A
NG_016193.2:g.58200G>T
NM_000411.8:c.250G>T
NM_001242784.3:c.250G>T
NM_001242785.2:c.250G>T
NM_001352514.2:c.691G>TMANE SELECT
NM_001352515.2:c.250G>T
NM_001352516.2:c.250G>T
NM_001352517.1:c.250G>T
NM_001352518.2:c.250G>T
NP_000402.3:p.Glu84Ter
NP_001229713.1:p.Glu84Ter
NP_001229714.1:p.Glu84Ter
NP_001339443.1:p.Glu231Ter
NP_001339444.1:p.Glu84Ter
NP_001339445.1:p.Glu84Ter
NP_001339446.1:p.Glu84Ter
NP_001339447.1:p.Glu84Ter
NC_000021.8:g.38309495C>A
NM_000411.6:c.250G>T
NR_148020.2:n.550G>T
NR_148021.1:n.707G>T

Protein change:

E231*

Links:

dbSNP: rs1569218416

NCBI 1000 Genomes Browser:

rs1569218416

Molecular consequence:

NR_148020.2:n.550G>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_148021.1:n.707G>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NM_000411.8:c.250G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001242784.3:c.250G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001242785.2:c.250G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001352514.2:c.691G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001352515.2:c.250G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001352516.2:c.250G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001352517.1:c.250G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001352518.2:c.250G>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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000830914	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Apr 9, 2020)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 16134170, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000830914

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Apr 9, 2020)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical 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 Labcorp Genetics (formerly Invitae), Labcorp, SCV000830914.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This sequence change creates a premature translational stop signal (p.Glu84*) in the HLCS gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with HLCS-related disease. Loss-of-function variants in HLCS are known to be pathogenic (PMID: 16134170). For these reasons, this variant has been classified as Pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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