NM_000017.4(ACADS):c.328G>A (p.Ala110Thr) AND Deficiency of butyryl-CoA dehydrogenase

Germline classification:: Conflicting interpretations of pathogenicity (3 submissions)
Last evaluated:: Sep 19, 2022
Review status:: criteria provided, conflicting classifications

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:: RCV000671132.12

Allele description [Variation Report for NM_000017.4(ACADS):c.328G>A (p.Ala110Thr)]

NM_000017.4(ACADS):c.328G>A (p.Ala110Thr)

Gene:

ACADS:acyl-CoA dehydrogenase short chain [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

12q24.31

Genomic location:

Preferred name:

NM_000017.4(ACADS):c.328G>A (p.Ala110Thr)

HGVS:

NC_000012.12:g.120737103G>A
NG_007991.1:g.16336G>A
NM_000017.4:c.328G>AMANE SELECT
NM_001302554.2:c.328G>A
NP_000008.1:p.Ala110Thr
NP_001289483.1:p.Ala110Thr
NC_000012.11:g.121174906G>A
NM_000017.2:c.328G>A
NM_000017.3:c.328G>A

Protein change:

A110T

Links:

dbSNP: rs780571371

NCBI 1000 Genomes Browser:

rs780571371

Molecular consequence:

NM_000017.4:c.328G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001302554.2:c.328G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Deficiency of butyryl-CoA dehydrogenase (ACADSD)
Synonyms:: ACYL-CoA DEHYDROGENASE, SHORT-CHAIN, DEFICIENCY OF; Lipid-storage myopathy secondary to short chain acyl CoA dehydrogenase deficiency; SCAD DEFICIENCY, MILD
Identifiers:: MONDO: MONDO:0008722; MedGen: C0342783; Orphanet: 26792; OMIM: 201470

Recent activity

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tyrosine-protein kinase receptor Tie-1 isoform 1 precursor [Homo sapiens]
tyrosine-protein kinase receptor Tie-1 isoform 1 precursor [Homo sapiens]
gi|4885631|ref|NP_005415.1|

Protein
histidine kinase [Chryseobacterium piperi]
histidine kinase [Chryseobacterium piperi]
gi|1239680751|gb|ASW74306.1||gnl|PR 2323|CJF12_08370

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000796078	Counsyl	no assertion criteria provided	Uncertain significance (Dec 7, 2017)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001391211	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Sep 19, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002033238	Genome-Nilou Lab	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Nov 7, 2021)	germline	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

SCV000796078

Counsyl

no assertion criteria provided

Uncertain significance
(Dec 7, 2017)

unknown

clinical testing

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

SCV001391211

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Sep 19, 2022)

germline

clinical testing

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

SCV002033238

Genome-Nilou Lab

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Nov 7, 2021)

germline

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	germline	no	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Mitochondrial fatty acid oxidation defects--remaining challenges.

Gregersen N, Andresen BS, Pedersen CB, Olsen RK, Corydon TJ, Bross P.

J Inherit Metab Dis. 2008 Oct;31(5):643-57. doi: 10.1007/s10545-008-0990-y. Epub 2008 Oct 7.

PubMed [citation]

PMID:: 18836889

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

See all PubMed Citations (3)

Details of each submission

From Counsyl, SCV000796078.2

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

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

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001391211.5

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

Description

This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 110 of the ACADS protein (p.Ala110Thr). 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 432099). This variant has not been reported in the literature in individuals affected with ACADS-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database.

#	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

From Genome-Nilou Lab, SCV002033238.1

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	no	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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