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NM_001352514.2(HLCS):c.569_585delinsTTGCTTGAGATTAAGCCTGAGATTAAGG (p.Pro190_Ser195delinsLeuAlaTer) AND Holocarboxylase synthetase deficiency

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Dec 16, 2022
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:
RCV002509407.1

Allele description [Variation Report for NM_001352514.2(HLCS):c.569_585delinsTTGCTTGAGATTAAGCCTGAGATTAAGG (p.Pro190_Ser195delinsLeuAlaTer)]

NM_001352514.2(HLCS):c.569_585delinsTTGCTTGAGATTAAGCCTGAGATTAAGG (p.Pro190_Ser195delinsLeuAlaTer)

Gene:
HLCS:holocarboxylase synthetase [Gene - OMIM - HGNC]
Variant type:
Indel
Cytogenetic location:
21q22.13
Genomic location:
Preferred name:
NM_001352514.2(HLCS):c.569_585delinsTTGCTTGAGATTAAGCCTGAGATTAAGG (p.Pro190_Ser195delinsLeuAlaTer)
HGVS:
  • NC_000021.9:g.36937301_36937317delinsCCTTAATCTCAGGCTTAATCTCAAGCAA
  • NG_016193.2:g.58078_58094delinsTTGCTTGAGATTAAGCCTGAGATTAAGG
  • NM_000411.8:c.128_144delinsTTGCTTGAGATTAAGCCTGAGATTAAGG
  • NM_001242784.3:c.128_144delinsTTGCTTGAGATTAAGCCTGAGATTAAGG
  • NM_001242785.2:c.128_144delinsTTGCTTGAGATTAAGCCTGAGATTAAGG
  • NM_001352514.2:c.569_585delinsTTGCTTGAGATTAAGCCTGAGATTAAGGMANE SELECT
  • NM_001352515.2:c.128_144delinsTTGCTTGAGATTAAGCCTGAGATTAAGG
  • NM_001352516.2:c.128_144delinsTTGCTTGAGATTAAGCCTGAGATTAAGG
  • NM_001352517.1:c.128_144delinsTTGCTTGAGATTAAGCCTGAGATTAAGG
  • NM_001352518.2:c.128_144delinsTTGCTTGAGATTAAGCCTGAGATTAAGG
  • NP_000402.3:p.Pro43_Ser48delinsLeuAlaTer
  • NP_001229713.1:p.Pro43_Ser48delinsLeuAlaTer
  • NP_001229714.1:p.Pro43_Ser48delinsLeuAlaTer
  • NP_001339443.1:p.Pro190_Ser195delinsLeuAlaTer
  • NP_001339444.1:p.Pro43_Ser48delinsLeuAlaTer
  • NP_001339445.1:p.Pro43_Ser48delinsLeuAlaTer
  • NP_001339446.1:p.Pro43_Ser48delinsLeuAlaTer
  • NP_001339447.1:p.Pro43_Ser48delinsLeuAlaTer
  • NC_000021.8:g.38309601_38309617delinsCCTTAATCTCAGGCTTAATCTCAAGCAA
  • NM_000411.6:c.128_144delinsTTGCTTGAGATTAAGCCTGAGATTAAGG
  • NR_148020.2:n.428_444delinsTTGCTTGAGATTAAGCCTGAGATTAAGG
  • NR_148021.1:n.585_601delinsTTGCTTGAGATTAAGCCTGAGATTAAGG
Links:
dbSNP: rs1064796014
NCBI 1000 Genomes Browser:
rs1064796014
Molecular consequence:
  • NR_148020.2:n.428_444delinsTTGCTTGAGATTAAGCCTGAGATTAAGG - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_148021.1:n.585_601delinsTTGCTTGAGATTAAGCCTGAGATTAAGG - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NM_000411.8:c.128_144delinsTTGCTTGAGATTAAGCCTGAGATTAAGG - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001242784.3:c.128_144delinsTTGCTTGAGATTAAGCCTGAGATTAAGG - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001242785.2:c.128_144delinsTTGCTTGAGATTAAGCCTGAGATTAAGG - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001352514.2:c.569_585delinsTTGCTTGAGATTAAGCCTGAGATTAAGG - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001352515.2:c.128_144delinsTTGCTTGAGATTAAGCCTGAGATTAAGG - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001352516.2:c.128_144delinsTTGCTTGAGATTAAGCCTGAGATTAAGG - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001352517.1:c.128_144delinsTTGCTTGAGATTAAGCCTGAGATTAAGG - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001352518.2:c.128_144delinsTTGCTTGAGATTAAGCCTGAGATTAAGG - 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

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Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002819603Women's Health and Genetics/Laboratory Corporation of America, LabCorp
criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)		Likely pathogenic
(Dec 16, 2022) 		germlineclinical testing

Citation Link

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Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV002819603.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

Variant summary: HLCS c.128_144delinsTTGCTTGAGATTAAGCCTGAGATTAAGG (p.Pro43LeufsX3) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 249914 control chromosomes (gnomAD). To our knowledge, no occurrence of c.128_144delins28 in individuals affected with Holocarboxylase Synthetase Deficiency and no experimental evidence demonstrating its impact on protein function have been reported. One ClinVar submitter has assessed the variant since 2014: the variant was classified as likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic.

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

Last Updated: Feb 7, 2023