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NM_015506.3(MMACHC):c.609G>A (p.Trp203Ter) AND not provided

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jul 25, 2017
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
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:
RCV000756343.12

Allele description [Variation Report for NM_015506.3(MMACHC):c.609G>A (p.Trp203Ter)]

NM_015506.3(MMACHC):c.609G>A (p.Trp203Ter)

Genes:
LOC129930446:ATAC-STARR-seq lymphoblastoid active region 972 [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.609G>A (p.Trp203Ter)
HGVS:
  • NC_000001.11:g.45508975G>A
  • NG_013378.1:g.13792G>A
  • NM_001330540.2:c.438G>A
  • NM_015506.3:c.609G>AMANE SELECT
  • NP_001317469.1:p.Trp146Ter
  • NP_056321.2:p.Trp203Ter
  • NC_000001.10:g.45974647G>A
  • NM_015506.2:c.609G>A
  • p.Trp203*
Protein change:
W146*; TRP203TER
Links:
OMIM: 609831.0006; dbSNP: rs587776889
NCBI 1000 Genomes Browser:
rs587776889
Molecular consequence:
  • NM_001330540.2:c.438G>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_015506.3:c.609G>A - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Synonyms:
none provided
Identifiers:
MedGen: C3661900

Assertion and evidence details

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Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000884123ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
criteria provided, single submitter

(ARUP Molecular Germline Variant Investigation Process)		Pathogenic
(Jul 25, 2017) 		germlineclinical testing

Citation Link

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Summary from all submissions

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

Details of each submission

From ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories, SCV000884123.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The p.Trp203Ter variant creates a termination codon in the MMACHC protein at codon 203 in exon 4 which is predicted to result in a truncated or absent protein product. In a cohort of 204 individuals suspected with inborn errors in cobalamin metabolism, the p.Trp203Ter was identified in the MMACHC gene from 7 individuals with pathogenic bi-allelic variants, including 5 homozygotes (Lerner-Ellis et. al. 2006). Furthermore, the p.Trp203Ter was observed in 52 out of 71 Chinese patients, including 15 homozygotes with elevated methylmalonic aciduria (MMA) and homocystinuria (HC), whereby haplotype analysis determined that it may have been caused by a founder effect in this population (Liu et. al. 2010). This variant is reported in ClinVar (Variation ID: 30800) as pathogenic. It is listed in the Genome Aggregation Database (gnomAD) with an overall population frequency of 0.004 percent (identified on 10 out of 246,224 chromosomes). Based on these observations the p.Trp203Ter is pathogenic.

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

Last Updated: Jun 23, 2024