NM_015506.3(MMACHC):c.316G>A (p.Glu106Lys) AND Cobalamin C disease

Clinical significance:Uncertain significance (Last evaluated: Dec 20, 2019)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
3 submissions [Details]
Record status:
current
Accession:
RCV000552788.6

Allele description [Variation Report for NM_015506.3(MMACHC):c.316G>A (p.Glu106Lys)]

NM_015506.3(MMACHC):c.316G>A (p.Glu106Lys)

Gene:
MMACHC:metabolism of cobalamin associated C [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
1p34.1
Genomic location:
Preferred name:
NM_015506.3(MMACHC):c.316G>A (p.Glu106Lys)
Other names:
p.E106K:GAG>AAG
HGVS:
  • NC_000001.11:g.45508251G>A
  • NG_013378.1:g.13068G>A
  • NM_001330540.2:c.145G>A
  • NM_015506.3:c.316G>AMANE SELECT
  • NP_001317469.1:p.Glu49Lys
  • NP_056321.2:p.Glu106Lys
  • NC_000001.10:g.45973923G>A
  • NM_015506.2:c.316G>A
Protein change:
E106K
Links:
dbSNP: rs201617713
NCBI 1000 Genomes Browser:
rs201617713
Molecular consequence:
  • NM_001330540.2:c.145G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_015506.3:c.316G>A - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

Condition(s)

Name:
Cobalamin C disease (MAHCC)
Synonyms:
Cobalamin-C methylmalonic acidemia and homocystinuria; Methylmalonic acidemia and homocystinuria cblC type; Methylmalonic aciduria and homocystinuria, Vitamin B12-responsive; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0010184; MedGen: C1848561; Orphanet: 26; Orphanet: 79282; OMIM: 277400

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000640286Invitaecriteria provided, single submitter
Uncertain significance
(Dec 20, 2019)
germlineclinical testing

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

SCV000923541Genomic Research Center,Shahid Beheshti University of Medical Sciencescriteria provided, single submitter
Uncertain significance
(Jan 1, 2019)
inheritedclinical testing

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

SCV001135277Mendelicscriteria provided, single submitter
Uncertain significance
(May 28, 2019)
unknownclinical testing

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing
not providedinheritedyes1not providednot providednot providednot providedclinical testing
not providedunknownunknownnot 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

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From Invitae, SCV000640286.3

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

Description

This sequence change replaces glutamic acid with lysine at codon 106 of the MMACHC protein (p.Glu106Lys). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is present in population databases (rs201617713, ExAC 0.06%) but has not been reported in the literature in individuals with a MMACHC-related disease. ClinVar contains an entry for this variant (Variation ID: 203826). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, this variant is a rare missense change with uncertain impact on protein function. Therefore, it has been classified as a Variant of Uncertain Significance.

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

From Genomic Research Center,Shahid Beheshti University of Medical Sciences, SCV000923541.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1inheritedyesnot providednot providednot provided1not providednot providednot provided

From Mendelics, SCV001135277.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Oct 6, 2021

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