NM_015506.3(MMACHC):c.315C>G (p.Tyr105Ter) AND Cobalamin C disease

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Jan 7, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000669305.4

Allele description [Variation Report for NM_015506.3(MMACHC):c.315C>G (p.Tyr105Ter)]

NM_015506.3(MMACHC):c.315C>G (p.Tyr105Ter)

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.315C>G (p.Tyr105Ter)

HGVS:

NC_000001.11:g.45508250C>G
NG_013378.1:g.13067C>G
NM_001330540.2:c.144C>G
NM_015506.3:c.315C>GMANE SELECT
NP_001317469.1:p.Tyr48Ter
NP_056321.2:p.Tyr105Ter
NC_000001.10:g.45973922C>G
NM_015506.2:c.315C>G

Protein change:

Y105*

Links:

dbSNP: rs528744719

NCBI 1000 Genomes Browser:

rs528744719

Molecular consequence:

NM_001330540.2:c.144C>G - nonsense - [Sequence Ontology: SO:0001587]
NM_015506.3:c.315C>G - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Cobalamin C disease
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

Recent activity

Clear Turn Off Turn On

ribosomal protein S7, partial [Profundulus parentiae]
ribosomal protein S7, partial [Profundulus parentiae]
gi|2525212126|gb|WJL31644.1|

Protein

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000794047	Counsyl	criteria provided, single submitter (Counsyl Autosomal Recessive and X-Linked Classification Criteria (2018))	Pathogenic (Sep 13, 2017)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link,
SCV004193198	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jan 7, 2024)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004292317	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 2, 2023)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 16311595, 20631720, 29731766, 31998365, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000794047

Counsyl

criteria provided, single submitter

(Counsyl Autosomal Recessive and X-Linked Classification Criteria (2018))

Pathogenic
(Sep 13, 2017)

unknown

clinical testing

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

Citation Link,

SCV004193198

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Jan 7, 2024)

unknown

clinical testing

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

SCV004292317

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 2, 2023)

germline

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

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

Identification of the gene responsible for methylmalonic aciduria and homocystinuria, cblC type.

Lerner-Ellis JP, Tirone JC, Pawelek PD, Doré C, Atkinson JL, Watkins D, Morel CF, Fujiwara TM, Moras E, Hosack AR, Dunbar GV, Antonicka H, Forgetta V, Dobson CM, Leclerc D, Gravel RA, Shoubridge EA, Coulton JW, Lepage P, Rommens JM, Morgan K, Rosenblatt DS.

Nat Genet. 2006 Jan;38(1):93-100. Epub 2005 Nov 27. Erratum in: Nat Genet. 2006 Aug;38(8):957.

PubMed [citation]

PMID:: 16311595

See all PubMed Citations (6)

Details of each submission

From Counsyl, SCV000794047.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Baylor Genetics, SCV004193198.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Invitae, SCV004292317.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This sequence change creates a premature translational stop signal (p.Tyr105*) in the MMACHC gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MMACHC are known to be pathogenic (PMID: 16311595). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with combined methylmalonic aciduria and homocystinuria (PMID: 20631720, 29731766, 31998365). ClinVar contains an entry for this variant (Variation ID: 553788). For these reasons, this variant has been classified as Pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Jun 17, 2024

ClinVar

Relating variation to medicine