NM_020166.5(MCCC1):c.863A>G (p.Glu288Gly) AND 3 Methylcrotonyl-CoA carboxylase 1 deficiency

Clinical significance:Uncertain significance (Last evaluated: Aug 18, 2016)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000549808.1

Allele description [Variation Report for NM_020166.5(MCCC1):c.863A>G (p.Glu288Gly)]

NM_020166.5(MCCC1):c.863A>G (p.Glu288Gly)

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.863A>G (p.Glu288Gly)
HGVS:
  • NC_000003.12:g.183057321T>C
  • NG_008100.1:g.47257A>G
  • NM_001293273.2:c.512A>G
  • NM_001363880.1:c.536A>G
  • NM_020166.5:c.863A>GMANE SELECT
  • NM_020166.5:c.863A>GMANE SELECT
  • NP_001280202.1:p.Glu171Gly
  • NP_001350809.1:p.Glu179Gly
  • NP_064551.3:p.Glu288Gly
  • NP_064551.3:p.Glu288Gly
  • NC_000003.11:g.182775109T>C
  • NM_020166.4:c.863A>G
  • NR_120639.2:n.686A>G
  • NR_120640.2:n.1530A>G
Protein change:
E171G
Links:
dbSNP: rs746500530
NCBI 1000 Genomes Browser:
rs746500530
Molecular consequence:
  • NM_001293273.2:c.512A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001363880.1:c.536A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_020166.5:c.863A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NR_120639.2:n.686A>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_120640.2:n.1530A>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
SCV000656961Invitaecriteria provided, single submitter
Uncertain significance
(Aug 18, 2016)
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, SCV000656961.1

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

Description

This sequence change replaces glutamic acid with glycine at codon 288 of the MCCC1 protein (p.Glu288Gly). The glutamic acid residue is highly conserved and there is a moderate physicochemical difference between glutamic acid and glycine. This variant is present in population databases (rs746500530, ExAC 0.04%). This variant has been reported in a homozygous individual with 3MCC deficiency who was reportedly asymptomatic at 7 years of age (PMID: 22642865). Experimental studies have shown that this missense change impairs the activity of the encoded enzyme (PMID: 22642865). In summary, this is a rare missense variant has been observed in the general population as well as reported in an individual with 3MCC deficiency.  Experimental data supports that this variant disrupts protein function, however, additional genetic evidence is needed to ascertain the clinical relevance of this variant. For these reasons, this change has been classified as a Variant of Uncertain Significance.

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

Last Updated: Oct 24, 2021

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