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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001232359	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 22, 2020)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 10590022, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001232359

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 22, 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

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

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical 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.

#	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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