NM_001243279.3(ACSF3):c.1491del (p.Ser498fs) AND Combined malonic and methylmalonic acidemia

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jul 19, 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:: RCV002839225.3

Allele description [Variation Report for NM_001243279.3(ACSF3):c.1491del (p.Ser498fs)]

NM_001243279.3(ACSF3):c.1491del (p.Ser498fs)

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.1491del (p.Ser498fs)

HGVS:

NC_000016.10:g.89145391del
NG_031961.1:g.56583del
NM_001127214.4:c.1491del
NM_001243279.3:c.1491delMANE SELECT
NM_001284316.2:c.696del
NM_174917.5:c.1491del
NP_001120686.1:p.Ser498fs
NP_001230208.1:p.Ser498fs
NP_001271245.1:p.Ser233fs
NP_777577.2:p.Ser498fs
NC_000016.9:g.89211796del
NC_000016.9:g.89211799del
NR_023316.2:n.1009delC
NR_045667.2:n.617del
NR_104293.2:n.1882del
NR_147928.2:n.1926del
NR_147929.2:n.1680del

Protein change:

S233fs

Molecular consequence:

NM_001127214.4:c.1491del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001243279.3:c.1491del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001284316.2:c.696del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_174917.5:c.1491del - frameshift variant - [Sequence Ontology: SO:0001589]
NR_045667.2:n.617del - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_104293.2:n.1882del - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_147928.2:n.1926del - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_147929.2:n.1680del - 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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003212607	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jul 19, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 21841779, 26827111, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003212607

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jul 19, 2022)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

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

Exome sequencing identifies ACSF3 as a cause of combined malonic and methylmalonic aciduria.

Sloan JL, Johnston JJ, Manoli I, Chandler RJ, Krause C, Carrillo-Carrasco N, Chandrasekaran SD, Sysol JR, O'Brien K, Hauser NS, Sapp JC, Dorward HM, Huizing M; NIH Intramural Sequencing Center Group., Barshop BA, Berry SA, James PM, Champaigne NL, de Lonlay P, Valayannopoulos V, Geschwind MD, Gavrilov DK, et al.

Nat Genet. 2011 Aug 14;43(9):883-6. doi: 10.1038/ng.908.

PubMed [citation]

PMID:: 21841779
PMCID:: PMC3163731

Added value of next generation gene panel analysis for patients with elevated methylmalonic acid and no clinical diagnosis following functional studies of vitamin B12 metabolism.

Pupavac M, Tian X, Chu J, Wang G, Feng Y, Chen S, Fenter R, Zhang VW, Wang J, Watkins D, Wong LJ, Rosenblatt DS.

Mol Genet Metab. 2016 Mar;117(3):363-8. doi: 10.1016/j.ymgme.2016.01.008. Epub 2016 Jan 23.

PubMed [citation]

PMID:: 26827111

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003212607.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This variant has not been reported in the literature in individuals affected with ACSF3-related conditions. For these reasons, this variant has been classified as Pathogenic. This variant is present in population databases (no rsID available, gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ser498Alafs*7) in the ACSF3 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ACSF3 are known to be pathogenic (PMID: 21841779, 26827111).

#	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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