NM_002435.3(MPI):c.61A>G (p.Met21Val) AND MPI-congenital disorder of glycosylation

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Oct 17, 2022
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:: RCV000821114.6

Allele description [Variation Report for NM_002435.3(MPI):c.61A>G (p.Met21Val)]

NM_002435.3(MPI):c.61A>G (p.Met21Val)

Gene:

MPI:mannose phosphate isomerase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

15q24.1

Genomic location:

Preferred name:

NM_002435.3(MPI):c.61A>G (p.Met21Val)

HGVS:

NC_000015.10:g.74890571A>G
NG_008921.1:g.5503A>G
NM_001289155.2:c.61A>G
NM_001289156.2:c.-7+482A>G
NM_001289157.2:c.61A>G
NM_001330372.2:c.1A>G
NM_002435.3:c.61A>GMANE SELECT
NP_001276084.1:p.Met21Val
NP_001276086.1:p.Met21Val
NP_001317301.1:p.Met1Val
NP_002426.1:p.Met21Val
NC_000015.9:g.75182912A>G
NM_001330372.1:c.1A>G
NM_002435.1:c.61A>G
NM_002435.2:c.61A>G

Protein change:

M1V

Links:

dbSNP: rs376746368

NCBI 1000 Genomes Browser:

rs376746368

Molecular consequence:

NM_001330372.2:c.1A>G - initiator_codon_variant - [Sequence Ontology: SO:0001582]
NM_001289156.2:c.-7+482A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001289155.2:c.61A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001289157.2:c.61A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001330372.2:c.1A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_002435.3:c.61A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: MPI-congenital disorder of glycosylation
Synonyms:: CONGENITAL DISORDER OF GLYCOSYLATION, TYPE Ib; CDG Ib; Congenital disorder of glycosylation type 1B; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0011257; MedGen: C1865145; Orphanet: 79319; OMIM: 602579

Recent activity

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integrin beta-7 isoform c precursor [Homo sapiens]
integrin beta-7 isoform c precursor [Homo sapiens]
gi|2329049477|ref|NP_001401094.1|

Protein
stil STIL centriolar assembly protein [Danio rerio]
stil STIL centriolar assembly protein [Danio rerio]
Gene ID:192317

Gene
192317[uid] AND (alive[prop]) (1)
Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000961858	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Oct 17, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002776780	Fulgent Genetics, Fulgent Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Jul 11, 2021)	unknown	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

SCV000961858

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Oct 17, 2022)

germline

clinical testing

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

SCV002776780

Fulgent Genetics, Fulgent Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Jul 11, 2021)

unknown

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	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
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

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 Labcorp Genetics (formerly Invitae), Labcorp, SCV000961858.5

#	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 methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 21 of the MPI protein (p.Met21Val). This variant is present in population databases (rs376746368, gnomAD 0.2%). This variant has not been reported in the literature in individuals affected with MPI-related conditions. ClinVar contains an entry for this variant (Variation ID: 663264). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The valine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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

From Fulgent Genetics, Fulgent Genetics, SCV002776780.2

#	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

Last Updated: Oct 13, 2024

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