NM_000018.4(ACADVL):c.1678+4A>T AND Very long chain acyl-CoA dehydrogenase deficiency

Germline classification:: Uncertain significance (3 submissions)
Last evaluated:: Oct 5, 2022
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV001049810.8

Allele description [Variation Report for NM_000018.4(ACADVL):c.1678+4A>T]

NM_000018.4(ACADVL):c.1678+4A>T

Gene:

ACADVL:acyl-CoA dehydrogenase very long chain [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

17p13.1

Genomic location:

Preferred name:

NM_000018.4(ACADVL):c.1678+4A>T

HGVS:

NC_000017.11:g.7224556A>T
NG_007975.1:g.9723A>T
NG_008391.2:g.495T>A
NG_033038.1:g.14989T>A
NM_000018.4:c.1678+4A>TMANE SELECT
NM_001033859.3:c.1612+4A>T
NM_001270447.2:c.1747+4A>T
NM_001270448.2:c.1450+4A>T
NC_000017.10:g.7127875A>T
NM_000018.2:c.1678+4A>T
NM_000018.3:c.1678+4A>T

Links:

dbSNP: rs1057518417

NCBI 1000 Genomes Browser:

rs1057518417

Molecular consequence:

NM_000018.4:c.1678+4A>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001033859.3:c.1612+4A>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001270447.2:c.1747+4A>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001270448.2:c.1450+4A>T - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Name:: Very long chain acyl-CoA dehydrogenase deficiency (ACADVLD)
Synonyms:: VLCAD deficiency
Identifiers:: MONDO: MONDO:0008723; MedGen: C3887523; Orphanet: 26793; OMIM: 201475

Recent activity

Clear Turn Off Turn On

type I polyketide synthase, partial [Streptomyces sp. MK37H]
type I polyketide synthase, partial [Streptomyces sp. MK37H]
gi|2027767334|ref|WP_210951550.1|

Protein
Cardiophorus convexus voucher BIOUG23409-E11 cytochrome oxidase subunit 1 (COI) ...
Cardiophorus convexus voucher BIOUG23409-E11 cytochrome oxidase subunit 1 (COI) gene, partial cds; mitochondrial
gi|1345516952|gnl|uoguelph|RRMFI422 COI-5P|gb|MG055049.1|

Nucleotide
UNVERIFIED: Pampus argenteus isolate yin34 ribosomal protein S7-like gene, parti...
UNVERIFIED: Pampus argenteus isolate yin34 ribosomal protein S7-like gene, partial sequence
gi|2736029938|gb|OR540906.1|

Nucleotide
UNVERIFIED: Pampus argenteus isolate yin39 ribosomal protein S7-like gene, parti...
UNVERIFIED: Pampus argenteus isolate yin39 ribosomal protein S7-like gene, partial sequence
gi|2736029943|gb|OR540911.1|

Nucleotide

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001213882	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Oct 5, 2022)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 30194637, 17576681, 9536098, 28492532
SCV001365120	Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Nov 1, 2019)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002088810	Natera, Inc.	no assertion criteria provided	Uncertain significance (Jul 27, 2020)	germline	clinical testing

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001213882

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Oct 5, 2022)

germline

clinical testing

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

SCV001365120

Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Nov 1, 2019)

germline

clinical testing

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

SCV002088810

Natera, Inc.

no assertion criteria provided

Uncertain significance
(Jul 27, 2020)

germline

clinical testing

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

The diagnostic challenge in very-long chain acyl-CoA dehydrogenase deficiency (VLCADD).

Hesse J, Braun C, Behringer S, Matysiak U, Spiekerkoetter U, Tucci S.

J Inherit Metab Dis. 2018 Nov;41(6):1169-1178. doi: 10.1007/s10545-018-0245-5. Epub 2018 Sep 7.

PubMed [citation]

PMID:: 30194637

Aberrant 5' splice sites in human disease genes: mutation pattern, nucleotide structure and comparison of computational tools that predict their utilization.

Buratti E, Chivers M, Královicová J, Romano M, Baralle M, Krainer AR, Vorechovsky I.

Nucleic Acids Res. 2007;35(13):4250-63. Epub 2007 Jun 18.

PubMed [citation]

PMID:: 17576681
PMCID:: PMC1934990

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001213882.3

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

Description

This sequence change falls in intron 17 of the ACADVL gene. It does not directly change the encoded amino acid sequence of the ACADVL protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (no rsID available, gnomAD 0.0009%). This variant has been observed in individual(s) with very long chain acyl-CoA dehydrogenase deficiency (PMID: 30194637). ClinVar contains an entry for this variant (Variation ID: 373435). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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.

#	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 Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine, SCV001365120.2

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

Description

The NM_000018.3:c.1678+4A>T (NP_000009.1:p.?) [GRCH38: NC_000017.11:g.7224556A>T] variant in ACADVL gene is interpretated to be Uncertain Significance based on ACMG guidelines (PMID: 25741868). This variant has been reported. This variant meets the following evidence codes reported in the ACMG guidelines: BP4

#	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 Natera, Inc., SCV002088810.1

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

#	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: Oct 20, 2024

ClinVar

Relating variation to medicine