NM_020166.5(MCCC1):c.1315G>A (p.Val439Met) AND 3 Methylcrotonyl-CoA carboxylase 1 deficiency

Clinical significance:Likely pathogenic (Last evaluated: Sep 20, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000653496.3

Allele description [Variation Report for NM_020166.5(MCCC1):c.1315G>A (p.Val439Met)]

NM_020166.5(MCCC1):c.1315G>A (p.Val439Met)

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.1315G>A (p.Val439Met)
HGVS:
  • NC_000003.12:g.183039088C>T
  • NG_008100.1:g.65490G>A
  • NM_001293273.1:c.964G>A
  • NM_001363880.1:c.988G>A
  • NM_020166.5:c.1315G>AMANE SELECT
  • NP_001280202.1:p.Val322Met
  • NP_001350809.1:p.Val330Met
  • NP_064551.3:p.Val439Met
  • NP_064551.3:p.Val439Met
  • NP_064551.3:p.Val439Met
  • NC_000003.11:g.182756876C>T
  • NM_020166.3:c.1315G>A
  • NM_020166.4:c.1315G>A
  • NR_120639.1:n.1229G>A
  • NR_120640.1:n.1982G>A
  • Q96RQ3:p.Val439Met
Protein change:
V322M
Links:
UniProtKB: Q96RQ3#VAR_072504; dbSNP: rs398124352
NCBI 1000 Genomes Browser:
rs398124352
Molecular consequence:
  • NM_001293273.1:c.964G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001363880.1:c.988G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_020166.5:c.1315G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NR_120639.1:n.1229G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_120640.1:n.1982G>A - 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
SCV000775376Invitaecriteria provided, single submitter
Likely pathogenic
(Sep 20, 2020)
germlineclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

3-methylcrotonyl-CoA carboxylase deficiency: clinical, biochemical, enzymatic and molecular studies in 88 individuals.

Grünert SC, Stucki M, Morscher RJ, Suormala T, Bürer C, Burda P, Christensen E, Ficicioglu C, Herwig J, Kölker S, Möslinger D, Pasquini E, Santer R, Schwab KO, Wilcken B, Fowler B, Yue WW, Baumgartner MR.

Orphanet J Rare Dis. 2012 May 29;7:31. doi: 10.1186/1750-1172-7-31.

PubMed [citation]
PMID:
22642865
PMCID:
PMC3495011

[Genetic analysis of newborns with abnormal metabolism of 3-hydroxyisovalerylcarnitine].

Wu D, Lu B, Yang J, Yang R, Huang X, Tong F, Zheng J, Zhao Z.

Zhejiang Da Xue Xue Bao Yi Xue Ban. 2019 Jun 25;48(4):390-396. Chinese.

PubMed [citation]
PMID:
31901042
See all PubMed Citations (3)

Details of each submission

From Invitae, SCV000775376.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

This sequence change replaces valine with methionine at codon 439 of the MCCC1 protein (p.Val439Met). The valine residue is highly conserved and there is a small physicochemical difference between valine and methionine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals with clinical features of 3-methylcrotonyl-CoA carboxylase deficiency (PMID: 22642865, 31901042, Invitae). ClinVar contains an entry for this variant (Variation ID: 95940). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: Deleterious; PolyPhen-2: Probably Damaging; Align-GVGD: Class C1). 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. 5

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

Last Updated: Oct 16, 2021

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