NM_052845.4(MMAB):c.554G>A (p.Cys185Tyr) AND Methylmalonic aciduria, cblB type

This record was updated by the submitter. Please see the current version.

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 27, 2021
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:: RCV001066216.6

Allele description

NM_052845.4(MMAB):c.554G>A (p.Cys185Tyr)

Gene:

MMAB:metabolism of cobalamin associated B [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

12q24.11

Genomic location:

Preferred name:

NM_052845.4(MMAB):c.554G>A (p.Cys185Tyr)

HGVS:

NC_000012.12:g.109561070C>T
NG_007096.1:g.17428G>A
NM_052845.4:c.554G>AMANE SELECT
NP_443077.1:p.Cys185Tyr
NC_000012.11:g.109998875C>T
NM_052845.3:c.554G>A
NR_038118.2:n.665G>A

Protein change:

C185Y

Links:

dbSNP: rs767774574

NCBI 1000 Genomes Browser:

rs767774574

Molecular consequence:

NM_052845.4:c.554G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_038118.2:n.665G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Methylmalonic aciduria, cblB type
Synonyms:: METHYLMALONIC ACIDURIA, VITAMIN B12-RESPONSIVE, DUE TO DEFECT IN SYNTHESIS OF ADENOSYLCOBALAMIN, cblB TYPE; Methylmalonic acidemia cblB type; Vitamin B12-responsive methylmalonic acidemia type cblB
Identifiers:: MONDO: MONDO:0009614; MedGen: C1855102; Orphanet: 28; Orphanet: 79311; OMIM: 251110

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001231221	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 27, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001231221

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 27, 2021)

germline

clinical testing

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

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

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. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV001231221.4

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

Description

This sequence change replaces cysteine with tyrosine at codon 185 of the MMAB protein (p.Cys185Tyr). The cysteine residue is moderately conserved and there is a large physicochemical difference between cysteine and tyrosine. This variant is present in population databases (rs767774574, ExAC 0.002%). This variant has not been reported in the literature in individuals affected with MMAB-related conditions. 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 C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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: Feb 7, 2023

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