NM_001609.4(ACADSB):c.443C>T (p.Thr148Ile) AND Inborn genetic diseases

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Jan 13, 2021
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:: RCV002512950.3

Allele description [Variation Report for NM_001609.4(ACADSB):c.443C>T (p.Thr148Ile)]

NM_001609.4(ACADSB):c.443C>T (p.Thr148Ile)

Gene:

ACADSB:acyl-CoA dehydrogenase short/branched chain [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

10q26.13

Genomic location:

Preferred name:

NM_001609.4(ACADSB):c.443C>T (p.Thr148Ile)

HGVS:

NC_000010.11:g.123040605C>T
NG_008003.1:g.36693C>T
NM_001330174.3:c.137C>T
NM_001609.4:c.443C>TMANE SELECT
NP_001317103.1:p.Thr46Ile
NP_001600.1:p.Thr148Ile
NP_001600.1:p.Thr148Ile
LRG_451t1:c.443C>T
LRG_451:g.36693C>T
LRG_451p1:p.Thr148Ile
NC_000010.10:g.124800121C>T
NM_001609.3:c.443C>T

Protein change:

T148I; THR148ILE

Links:

OMIM: 600301.0004; dbSNP: rs58639322

NCBI 1000 Genomes Browser:

rs58639322

Molecular consequence:

NM_001330174.3:c.137C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001609.4:c.443C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Inborn genetic diseases
Identifiers:: MeSH: D030342; MedGen: C0950123

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003741195	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Likely pathogenic (Jan 13, 2021)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 15615815, 17945527, 20547083, 30730842 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003741195

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Likely pathogenic
(Jan 13, 2021)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

Citation Link

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

2-ethylhydracrylic aciduria in short/branched-chain acyl-CoA dehydrogenase deficiency: application to diagnosis and implications for the R-pathway of isoleucine oxidation.

Korman SH, Andresen BS, Zeharia A, Gutman A, Boneh A, Pitt JJ.

Clin Chem. 2005 Mar;51(3):610-7. Epub 2004 Dec 22.

PubMed [citation]

PMID:: 15615815

2-Methylbutyryl-coenzyme A dehydrogenase deficiency: functional and molecular studies on a defect in isoleucine catabolism.

Sass JO, Ensenauer R, Röschinger W, Reich H, Steuerwald U, Schirrmacher O, Engel K, Häberle J, Andresen BS, Mégarbané A, Lehnert W, Zschocke J.

Mol Genet Metab. 2008 Jan;93(1):30-5. Epub 2007 Oct 22.

PubMed [citation]

PMID:: 17945527

See all PubMed Citations (4)

Details of each submission

From Ambry Genetics, SCV003741195.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

The c.443C>T (p.T148I) alteration is located in exon 4 (coding exon 4) of the ACADSB gene. This alteration results from a C to T substitution at nucleotide position 443, causing the threonine (T) at amino acid position 148 to be replaced by an isoleucine (I). This variant has been reported in individuals with biochemical evidence of 2-methylbutyrylglycinuria in both the homozygous and compound heterozygous state; however, most were reported as clinically asymptomatic (Korman, 2005; Sass, 2008; Alfardan, 2010; Porta, 2019). One individual presented with a history of metabolic acidosis and coma during illness (Porta, 2019). In E. coli with this variant, enzyme activity was reduced to 2.8% of wild type activity levels (Alfardan, 2010). The in silico prediction for the p.T148I alteration is inconclusive. Based on the available evidence, this alteration is classified as likely 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: Nov 18, 2024

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