NM_020166.5(MCCC1):c.1A>G (p.Met1Val) AND 3 Methylcrotonyl-CoA carboxylase 1 deficiency

Clinical significance:Likely pathogenic (Last evaluated: Dec 18, 2018)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000653495.2

Allele description [Variation Report for NM_020166.5(MCCC1):c.1A>G (p.Met1Val)]

NM_020166.5(MCCC1):c.1A>G (p.Met1Val)

Gene:
MCCC1:methylcrotonyl-CoA carboxylase subunit 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
3q27.1
Genomic location:
Preferred name:
NM_020166.5(MCCC1):c.1A>G (p.Met1Val)
HGVS:
  • NC_000003.12:g.183099440T>C
  • NG_008100.1:g.5138A>G
  • NM_001293273.1:c.-92A>G
  • NM_001363880.1:c.-190A>G
  • NM_020166.5:c.1A>GMANE SELECT
  • NP_064551.3:p.Met1Val
  • NC_000003.11:g.182817228T>C
  • NM_020166.4:c.1A>G
  • NR_120639.1:n.148A>G
Protein change:
M1V
Links:
dbSNP: rs762463914
NCBI 1000 Genomes Browser:
rs762463914
Molecular consequence:
  • NM_001293273.1:c.-92A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001363880.1:c.-190A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_020166.5:c.1A>G - initiatior codon variant - [Sequence Ontology: SO:0001582]
  • NM_020166.5:c.1A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NR_120639.1:n.148A>G - 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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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000775375Invitaecriteria provided, single submitter
Likely pathogenic
(Dec 18, 2018)
germlineclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical 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):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV000775375.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

This sequence change affects the initiator methionine of the MCCC1 mRNA. The next in-frame methionine is located at codon 39. This variant is present in population databases (rs762463914, ExAC 0.02%). This variant has been observed as homozygous in an individual with elevated 3-methylcrotonylglycine, findings that are highly specific for 3-MCC deficiency (Invitae). Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the deleted amino acids is currently unknown. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Apr 18, 2021

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