NM_001243279.3(ACSF3):c.1720del (p.His574fs) AND Combined malonic and methylmalonic acidemia

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Mar 12, 2022
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:: RCV002586865.3

Allele description [Variation Report for NM_001243279.3(ACSF3):c.1720del (p.His574fs)]

NM_001243279.3(ACSF3):c.1720del (p.His574fs)

Gene:

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

Variant type:

Deletion

Cytogenetic location:

16q24.3

Genomic location:

Preferred name:

NM_001243279.3(ACSF3):c.1720del (p.His574fs)

HGVS:

NC_000016.10:g.89154196del
NG_031961.1:g.65388del
NM_001127214.4:c.1720del
NM_001243279.3:c.1720delMANE SELECT
NM_001284316.2:c.925del
NM_174917.5:c.1720del
NP_001120686.1:p.His574fs
NP_001230208.1:p.His574fs
NP_001271245.1:p.His309fs
NP_777577.2:p.His574fs
NC_000016.9:g.89220603del
NC_000016.9:g.89220604del
NR_023316.2:n.1238delC
NR_045667.2:n.846del
NR_104293.2:n.2111del
NR_147928.2:n.2155del
NR_147929.2:n.1909del

Protein change:

H309fs

Molecular consequence:

NM_001127214.4:c.1720del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001243279.3:c.1720del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001284316.2:c.925del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_174917.5:c.1720del - frameshift variant - [Sequence Ontology: SO:0001589]
NR_045667.2:n.846del - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_104293.2:n.2111del - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_147928.2:n.2155del - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_147929.2:n.1909del - 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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RecName: Full=Creatine kinase U-type, mitochondrial; AltName: Full=Acidic-type m...
RecName: Full=Creatine kinase U-type, mitochondrial; AltName: Full=Acidic-type mitochondrial creatine kinase; Short=Mia-CK; AltName: Full=Ubiquitous mitochondrial creatine kinase; Short=U-MtCK; Flags: Precursor
gi|125315|sp|P12532.1|KCRU_HUMAN

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002943093	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Mar 12, 2022)	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

SCV002943093

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Mar 12, 2022)

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

Citations

PubMed

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 Labcorp Genetics (formerly Invitae), Labcorp, SCV002943093.2

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

Description

This variant has not been reported in the literature in individuals affected with ACSF3-related conditions. 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. This variant is present in population databases (no rsID available, gnomAD 0.003%). This sequence change results in a frameshift in the ACSF3 gene (p.His574Thrfs*98). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 3 amino acid(s) of the ACSF3 protein and extend the protein by 94 additional amino acid residues.

#	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: Sep 29, 2024

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