NM_144988.4(ALG14):c.288G>T (p.Met96Ile) AND Congenital myasthenic syndrome 15

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jan 1, 2023
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:: RCV003752267.2

Allele description [Variation Report for NM_144988.4(ALG14):c.288G>T (p.Met96Ile)]

NM_144988.4(ALG14):c.288G>T (p.Met96Ile)

Genes:

ALG14:ALG14 UDP-N-acetylglucosaminyltransferase subunit [Gene - OMIM - HGNC]
ALG14-AS1:ALG14 antisense RNA 1 [Gene - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1p21.3

Genomic location:

Preferred name:

NM_144988.4(ALG14):c.288G>T (p.Met96Ile)

HGVS:

NC_000001.11:g.95064866C>A
NG_042044.1:g.13086G>T
NG_042044.2:g.13085G>T
NM_001305242.2:c.288G>T
NM_144988.4:c.288G>TMANE SELECT
NP_001292171.1:p.Met96Ile
NP_659425.1:p.Met96Ile
NC_000001.10:g.95530422C>A

Protein change:

M96I

Molecular consequence:

NM_001305242.2:c.288G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_144988.4:c.288G>T - missense variant - [Sequence Ontology: SO:0001583]

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

Recent activity

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Mus musculus casein kinase 1, delta (Csnk1d), transcript variant 2, mRNA
Mus musculus casein kinase 1, delta (Csnk1d), transcript variant 2, mRNA
gi|2329049467|ref|NM_027874.3|

Nucleotide
Rab3 GTPase-activating protein catalytic subunit [Arabidopsis thaliana]
Rab3 GTPase-activating protein catalytic subunit [Arabidopsis thaliana]
gi|79537390|ref|NP_200317.2|

Protein
Homo sapiens EF-hand domain family, member D2, mRNA (cDNA clone MGC:87102 IMAGE:...
Homo sapiens EF-hand domain family, member D2, mRNA (cDNA clone MGC:87102 IMAGE:5267148), complete cds
gi|46250413|gb|BC068473.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004450116	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 1, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 17576681, 9536098, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004450116

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 1, 2023)

germline

clinical testing

PubMed (3)
[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

Citations

PubMed

Aberrant 5' splice sites in human disease genes: mutation pattern, nucleotide structure and comparison of computational tools that predict their utilization.

Buratti E, Chivers M, Královicová J, Romano M, Baralle M, Krainer AR, Vorechovsky I.

Nucleic Acids Res. 2007;35(13):4250-63. Epub 2007 Jun 18.

PubMed [citation]

PMID:: 17576681
PMCID:: PMC1934990

Statistical features of human exons and their flanking regions.

Zhang MQ.

Hum Mol Genet. 1998 May;7(5):919-32.

PubMed [citation]

PMID:: 9536098

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004450116.1

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

Description

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. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. This variant has not been reported in the literature in individuals affected with ALG14-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces methionine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 96 of the ALG14 protein (p.Met96Ile). This variant also falls at the last nucleotide of exon 2, which is part of the consensus splice site for this exon.

#	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: Sep 29, 2024

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