NM_020166.5(MCCC1):c.1522_1544del (p.Leu508fs) AND 3-methylcrotonyl-CoA carboxylase 1 deficiency

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jul 26, 2023
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:: RCV001043256.5

Allele description [Variation Report for NM_020166.5(MCCC1):c.1522_1544del (p.Leu508fs)]

NM_020166.5(MCCC1):c.1522_1544del (p.Leu508fs)

Gene:

MCCC1:methylcrotonyl-CoA carboxylase subunit 1 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

3q27.1

Genomic location:

Preferred name:

NM_020166.5(MCCC1):c.1522_1544del (p.Leu508fs)

HGVS:

NC_000003.12:g.183037272_183037294del
NG_008100.1:g.67288_67310del
NM_001293273.2:c.1171_1193del
NM_001363880.1:c.1195_1217del
NM_020166.5:c.1522_1544delMANE SELECT
NP_001280202.1:p.Leu391fs
NP_001350809.1:p.Leu399fs
NP_064551.3:p.Leu508fs
NC_000003.11:g.182755056_182755078del
NC_000003.11:g.182755060_182755082del
NM_020166.4:c.1522_1544del
NR_120639.2:n.1345_1367del

Protein change:

L391fs

Links:

dbSNP: rs1713693597

NCBI 1000 Genomes Browser:

rs1713693597

Molecular consequence:

NM_001293273.2:c.1171_1193del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001363880.1:c.1195_1217del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_020166.5:c.1522_1544del - frameshift variant - [Sequence Ontology: SO:0001589]
NR_120639.2:n.1345_1367del - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: 3-methylcrotonyl-CoA carboxylase 1 deficiency (MCC1D)
Synonyms:: MCCD TYPE 1; METHYLCROTONYLGLYCINURIA TYPE I; MCC 1 deficiency; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0008861; MedGen: C0268600; Orphanet: 6; OMIM: 210200

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001206982	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jul 26, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 11181649, 15359379, 22642865, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001206982

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jul 26, 2023)

germline

clinical testing

PubMed (4)
[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

The molecular basis of human 3-methylcrotonyl-CoA carboxylase deficiency.

Baumgartner MR, Almashanu S, Suormala T, Obie C, Cole RN, Packman S, Baumgartner ER, Valle D.

J Clin Invest. 2001 Feb;107(4):495-504.

PubMed [citation]

PMID:: 11181649
PMCID:: PMC199271

Isolated 3-methylcrotonyl-CoA carboxylase deficiency: evidence for an allele-specific dominant negative effect and responsiveness to biotin therapy.

Baumgartner MR, Dantas MF, Suormala T, Almashanu S, Giunta C, Friebel D, Gebhardt B, Fowler B, Hoffmann GF, Baumgartner ER, Valle D.

Am J Hum Genet. 2004 Nov;75(5):790-800. Epub 2004 Sep 9.

PubMed [citation]

PMID:: 15359379
PMCID:: PMC1182108

See all PubMed Citations (4)

Details of each submission

From Invitae, SCV001206982.5

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

Description

For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 841106). This variant has not been reported in the literature in individuals affected with MCCC1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Leu508Hisfs*17) in the MCCC1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MCCC1 are known to be pathogenic (PMID: 11181649, 15359379, 22642865).

#	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: Feb 28, 2024

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