NM_020166.5(MCCC1):c.1193_1194del (p.Val398fs) AND 3-methylcrotonyl-CoA carboxylase 1 deficiency

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: May 10, 2023
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:: RCV000687710.8

Allele description [Variation Report for NM_020166.5(MCCC1):c.1193_1194del (p.Val398fs)]

NM_020166.5(MCCC1):c.1193_1194del (p.Val398fs)

Gene:

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

Variant type:

Microsatellite

Cytogenetic location:

3q27.1

Genomic location:

Preferred name:

NM_020166.5(MCCC1):c.1193_1194del (p.Val398fs)

HGVS:

NC_000003.12:g.183041640CA[1]
NG_008100.1:g.62935TG[1]
NM_001293273.2:c.842_843del
NM_001363880.1:c.866_867del
NM_020166.5:c.1193_1194delMANE SELECT
NP_001280202.1:p.Val281fs
NP_001350809.1:p.Val289fs
NP_064551.3:p.Val398fs
NC_000003.11:g.182759428CA[1]
NC_000003.11:g.182759428_182759429del
NM_020166.3:c.1193_1194delTG
NM_020166.4:c.1193_1194delTG
NR_120639.2:n.1014TG[1]
NR_120640.2:n.1858TG[1]
p.V398GfsX19

Protein change:

V281fs

Links:

dbSNP: rs796051985

NCBI 1000 Genomes Browser:

rs796051985

Molecular consequence:

NM_001293273.2:c.842_843del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001363880.1:c.866_867del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_020166.5:c.1193_1194del - frameshift variant - [Sequence Ontology: SO:0001589]
NR_120639.2:n.1014TG[1] - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_120640.2:n.1858TG[1] - 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
SCV000815295	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Feb 17, 2022)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 11181649, 15359379, 22642865, 28492532
SCV004194282	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (May 10, 2023)	unknown	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

SCV000815295

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Feb 17, 2022)

germline

clinical testing

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

SCV004194282

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(May 10, 2023)

unknown

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	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
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 (5)

Details of each submission

From Invitae, SCV000815295.4

#	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. This sequence change creates a premature translational stop signal (p.Val398Glyfs*19) 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). This variant is present in population databases (rs796051985, gnomAD 0.002%). This premature translational stop signal has been observed in individual(s) with 3-methylcrotonyl-CoA carboxylase deficiency (PMID: 22642865). ClinVar contains an entry for this variant (Variation ID: 203798).

#	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 Baylor Genetics, SCV004194282.1

#	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	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Apr 15, 2024

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