NM_144988.4(ALG14):c.326G>A (p.Arg109Gln) AND Congenital myasthenic syndrome 15

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Apr 11, 2023
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:: RCV000688360.4

Allele description [Variation Report for NM_144988.4(ALG14):c.326G>A (p.Arg109Gln)]

NM_144988.4(ALG14):c.326G>A (p.Arg109Gln)

Gene:

ALG14:ALG14 UDP-N-acetylglucosaminyltransferase subunit [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1p21.3

Genomic location:

Preferred name:

NM_144988.4(ALG14):c.326G>A (p.Arg109Gln)

Other names:

ALG14, ARG109GLN (rs199689080)

HGVS:

NC_000001.11:g.95027223C>T
NG_042044.1:g.50729G>A
NM_001305242.2:c.363G>A
NM_144988.4:c.326G>AMANE SELECT
NP_001292171.1:p.Pro121=
NP_659425.1:p.Arg109Gln
NC_000001.10:g.95492779C>T
NM_144988.3:c.326G>A
NR_131032.2:n.227G>A

Protein change:

R109Q; ARG109GLN

Links:

OMIM: 612866.0006; dbSNP: rs199689080

NCBI 1000 Genomes Browser:

rs199689080

Molecular consequence:

NM_144988.4:c.326G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_131032.2:n.227G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NM_001305242.2:c.363G>A - synonymous variant - [Sequence Ontology: SO:0001819]

Condition(s)

Name:: Congenital myasthenic syndrome 15
Synonyms:: Myasthenic syndrome, congenital, 15, without tubular aggregates
Identifiers:: MONDO: MONDO:0014542; MedGen: C4015596; Orphanet: 353327; Orphanet: 590; OMIM: 616227

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000815968	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 23, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 28733338, 33751823, 28492532
SCV004049475	Genome-Nilou Lab	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Apr 11, 2023)	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

SCV000815968

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 23, 2022)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

SCV004049475

Genome-Nilou Lab

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Apr 11, 2023)

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	no	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

Early and lethal neurodegeneration with myasthenic and myopathic features: A new ALG14-CDG.

Schorling DC, Rost S, Lefeber DJ, Brady L, Müller CR, Korinthenberg R, Tarnopolsky M, Bönnemann CG, Rodenburg RJ, Bugiani M, Beytia M, Krüger M, van der Knaap M, Kirschner J.

Neurology. 2017 Aug 15;89(7):657-664. doi: 10.1212/WNL.0000000000004234. Epub 2017 Jul 21.

PubMed [citation]

PMID:: 28733338
PMCID:: PMC5562963

A novel ALG14 missense variant in an alive child with myopathy, epilepsy, and progressive cerebral atrophy.

Palombo F, Piccolo B, Saccani E, Fiorini C, Capristo M, Caporali L, Pisani F, Carelli V.

Am J Med Genet A. 2021 Jun;185(6):1918-1921. doi: 10.1002/ajmg.a.62153. Epub 2021 Mar 10. No abstract available.

PubMed [citation]

PMID:: 33751823

See all PubMed Citations (4)

Details of each submission

From Invitae, SCV000815968.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 109 of the ALG14 protein (p.Arg109Gln). This variant is present in population databases (rs199689080, gnomAD 0.01%). This missense change has been observed in individual(s) with clinical features of ALG14-congenital disorder of glycosylation (PMID: 28733338, 33751823). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 379351). 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

From Genome-Nilou Lab, SCV004049475.1

#	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	germline	no	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Dec 24, 2023

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