NM_014362.4(HIBCH):c.1128dup (p.Lys377Ter) AND Beta-hydroxyisobutyryl-CoA deacylase deficiency

Germline classification:: Likely pathogenic (2 submissions)
Last evaluated:: Mar 1, 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:: RCV000201262.3

Allele description [Variation Report for NM_014362.4(HIBCH):c.1128dup (p.Lys377Ter)]

NM_014362.4(HIBCH):c.1128dup (p.Lys377Ter)

Gene:

HIBCH:3-hydroxyisobutyryl-CoA hydrolase [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

2q32.2

Genomic location:

Preferred name:

NM_014362.4(HIBCH):c.1128dup (p.Lys377Ter)

HGVS:

NC_000002.12:g.190205152dup
NG_017062.1:g.119896dup
NM_014362.4:c.1128dupMANE SELECT
NM_198047.3:c.*77dup
NP_055177.2:p.Lys377Ter
NC_000002.11:g.191069878dup
NC_000002.12:g.190205150dup
NM_014362.2:c.1128dup
NM_014362.3:c.1128dup

Protein change:

K377*

Links:

OMIM: 610690.0008; dbSNP: rs863225062

NCBI 1000 Genomes Browser:

rs863225062

Molecular consequence:

NM_198047.3:c.*77dup - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_014362.4:c.1128dup - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Beta-hydroxyisobutyryl-CoA deacylase deficiency (HIBCHD)
Synonyms:: HIBCH DEFICIENCY; METHACRYLIC ACID TOXICITY; METHACRYLIC ACIDURIA; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0009603; MedGen: C0342738; Orphanet: 88639; OMIM: 250620

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000255994	OMIM	no assertion criteria provided	Pathogenic (Dec 1, 2014)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV001443057	Institute of Human Genetics, University of Leipzig Medical Center	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Mar 1, 2020)	biparental	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000255994

OMIM

no assertion criteria provided

Pathogenic
(Dec 1, 2014)

germline

literature only

PubMed (1)
[See all records that cite this PMID]

SCV001443057

Institute of Human Genetics, University of Leipzig Medical Center

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Mar 1, 2020)

biparental

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	biparental	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

HIBCH deficiency in a patient with phenotypic characteristics of mitochondrial disorders.

Reuter MS, Sass JO, Leis T, Köhler J, Mayr JA, Feichtinger RG, Rauh M, Schanze I, Bähr L, Trollmann R, Uebe S, Ekici AB, Reis A.

Am J Med Genet A. 2014 Dec;164A(12):3162-9. doi: 10.1002/ajmg.a.36766. Epub 2014 Sep 23.

PubMed [citation]

PMID:: 25251209

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

Details of each submission

From OMIM, SCV000255994.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

Description

In a 5-year-old boy, born of consanguineous Tunisian parents, with 3-hydroxyisobutyryl-CoA hydrolase deficiency (HIBCHD; 250620), Reuter et al. (2014) identified a homozygous 1-bp insertion (c.1128_1129insT, NM_014362.3) in the HIBCH gene, resulting in a frameshift and premature termination (Lys377Ter). The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family and was not found in the dbSNP, 1000 Genomes Project, or Exome Variant Server databases. Patient cells showed no detectable HIBCH enzymatic activity.

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

From Institute of Human Genetics, University of Leipzig Medical Center, SCV001443057.1

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

Description

Review of the variants reported in Reuter et al., 2017, PMID: 28097321: PVS1_Strong,PM2,PM3_Supporting

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

Last Updated: Feb 7, 2023

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