NM_001243279.3(ACSF3):c.1643C>T (p.Ser548Leu) AND Combined malonic and methylmalonic acidemia

This record was updated by the submitter. Please see the current version.

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Jul 14, 2021
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:: RCV001559235.3

Allele description

NM_001243279.3(ACSF3):c.1643C>T (p.Ser548Leu)

Gene:

ACSF3:acyl-CoA synthetase family member 3 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

16q24.3

Genomic location:

Preferred name:

NM_001243279.3(ACSF3):c.1643C>T (p.Ser548Leu)

HGVS:

NC_000016.10:g.89154119C>T
NG_031961.1:g.65311C>T
NM_001127214.4:c.1643C>T
NM_001243279.3:c.1643C>TMANE SELECT
NM_001284316.2:c.848C>T
NM_174917.5:c.1643C>T
NP_001120686.1:p.Ser548Leu
NP_001230208.1:p.Ser548Leu
NP_001271245.1:p.Ser283Leu
NP_777577.2:p.Ser548Leu
NC_000016.9:g.89220527C>T
NR_045667.2:n.769C>T
NR_104293.2:n.2034C>T
NR_147928.2:n.2078C>T
NR_147929.2:n.1832C>T

Protein change:

S283L

Links:

dbSNP: rs139520739

NCBI 1000 Genomes Browser:

rs139520739

Molecular consequence:

NM_001127214.4:c.1643C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001243279.3:c.1643C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001284316.2:c.848C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_174917.5:c.1643C>T - missense variant - [Sequence Ontology: SO:0001583]
NR_045667.2:n.769C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_104293.2:n.2034C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_147928.2:n.2078C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_147929.2:n.1832C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Combined malonic and methylmalonic acidemia
Synonyms:: Combined malonic and methylmalonic aciduria
Identifiers:: MONDO: MONDO:0013661; MedGen: C3280314; Orphanet: 289504; OMIM: 614265

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Cln3 protein [Mus musculus]
Cln3 protein [Mus musculus]
gi|51593739|gb|AAH80759.1|

Protein
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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001781379	Genome-Nilou Lab	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Jul 14, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV003250376	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jul 9, 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

SCV001781379

Genome-Nilou Lab

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Jul 14, 2021)

germline

clinical testing

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

SCV003250376

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jul 9, 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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	no	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

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

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

Details of each submission

From Genome-Nilou Lab, SCV001781379.1

#	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

From Invitae, SCV003250376.1

#	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 serine with leucine at codon 548 of the ACSF3 protein (p.Ser548Leu). The serine residue is weakly conserved and there is a large physicochemical difference between serine and leucine. This variant is present in population databases (rs139520739, ExAC 0.07%). This variant has not been reported in the literature in individuals affected with ACSF3-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). 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

Last Updated: Dec 24, 2023

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