NM_001352514.2(HLCS):c.1163G>C (p.Gly388Ala) AND Holocarboxylase synthetase deficiency

Clinical significance:Likely pathogenic (Last evaluated: Jul 21, 2015)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000408618.1

Allele description [Variation Report for NM_001352514.2(HLCS):c.1163G>C (p.Gly388Ala)]

NM_001352514.2(HLCS):c.1163G>C (p.Gly388Ala)

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.1163G>C (p.Gly388Ala)
HGVS:
  • NC_000021.9:g.36936723C>G
  • NG_016193.2:g.58672G>C
  • NM_000411.8:c.722G>C
  • NM_001242784.3:c.722G>C
  • NM_001242785.2:c.722G>C
  • NM_001352514.2:c.1163G>CMANE SELECT
  • NM_001352515.2:c.722G>C
  • NM_001352516.2:c.722G>C
  • NM_001352517.1:c.722G>C
  • NM_001352518.2:c.722G>C
  • NP_000402.3:p.Gly241Ala
  • NP_001229713.1:p.Gly241Ala
  • NP_001229714.1:p.Gly241Ala
  • NP_001339443.1:p.Gly388Ala
  • NP_001339444.1:p.Gly241Ala
  • NP_001339445.1:p.Gly241Ala
  • NP_001339446.1:p.Gly241Ala
  • NP_001339447.1:p.Gly241Ala
  • NC_000021.8:g.38309023C>G
  • NM_000411.6:c.722G>C
  • NR_148020.2:n.1022G>C
  • NR_148021.1:n.1179G>C
Protein change:
G241A
Links:
dbSNP: rs1057516035
NCBI 1000 Genomes Browser:
rs1057516035
Molecular consequence:
  • NM_000411.8:c.722G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001242784.3:c.722G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001242785.2:c.722G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001352514.2:c.1163G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001352515.2:c.722G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001352516.2:c.722G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001352517.1:c.722G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001352518.2:c.722G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NR_148020.2:n.1022G>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_148021.1:n.1179G>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
Observations:
1

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
SCV000484429Victorian Clinical Genetics Services,Murdoch Childrens Research Institutecriteria provided, single submitter
Likely pathogenic
(Jul 21, 2015)
inheritedclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedinheritedyes31not provided3yesclinical testing

Citations

PubMed

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

A prospective evaluation of whole-exome sequencing as a first-tier molecular test in infants with suspected monogenic disorders.

Stark Z, Tan TY, Chong B, Brett GR, Yap P, Walsh M, Yeung A, Peters H, Mordaunt D, Cowie S, Amor DJ, Savarirayan R, McGillivray G, Downie L, Ekert PG, Theda C, James PA, Yaplito-Lee J, Ryan MM, Leventer RJ, Creed E, Macciocca I, et al.

Genet Med. 2016 Nov;18(11):1090-1096. doi: 10.1038/gim.2016.1. Epub 2016 Mar 3.

PubMed [citation]
PMID:
26938784

Details of each submission

From Victorian Clinical Genetics Services,Murdoch Childrens Research Institute, SCV000484429.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided3not providedyesclinical testing PubMed (2)

Description

This homozygous variant was identified in a patient with biochemical features of HLCS deficiency. This substitution is predicted to result in a change of a glycine to an alanine at position 241, NP_00402.3, p.(Gly241Ala). The amino acid at this position is highly conserved, and in a functional domain (GAT_1, type 1 glutamine amidotransferase-like domain). This substitution is predicted to be disease-causing by in-silico models, and is novel. Another substitution at the same position, p.(Gly241Trp) has been reported as disease-causing in another family (De Castro et al 2015, JIMD 20:1-4).

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1inheritedyes3Bloodnot provided3not provided1not provided

Last Updated: Oct 24, 2021

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