NM_001244710.2(GFPT1):c.2055+3A>G AND Congenital myasthenic syndrome 12

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Dec 15, 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:: RCV000527468.7

Allele description [Variation Report for NM_001244710.2(GFPT1):c.2055+3A>G]

NM_001244710.2(GFPT1):c.2055+3A>G

Gene:

GFPT1:glutamine--fructose-6-phosphate transaminase 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2p13.3

Genomic location:

Preferred name:

NM_001244710.2(GFPT1):c.2055+3A>G

HGVS:

NC_000002.12:g.69326911T>C
NG_029542.1:g.65340A>G
NM_001244710.2:c.2055+3A>GMANE SELECT
NM_002056.4:c.2001+3A>G
LRG_787t1:c.2055+3A>G
LRG_787:g.65340A>G
NC_000002.11:g.69554043T>C
NM_001244710.1:c.2055+3A>G
NM_002056.3:c.2001+3A>G

Links:

dbSNP: rs937857366

NCBI 1000 Genomes Browser:

rs937857366

Molecular consequence:

NM_001244710.2:c.2055+3A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_002056.4:c.2001+3A>G - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Name:: Congenital myasthenic syndrome 12 (CMS12)
Synonyms:: MYASTHENIC SYNDROME, CONGENITAL, WITH TUBULAR AGGREGATES 1; Myasthenia, congenital, 12, with tubular aggregates
Identifiers:: MONDO: MONDO:0012518; MedGen: C3552335; Orphanet: 353327; Orphanet: 590; OMIM: 610542

Recent activity

Clear Turn Off Turn On

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
SCV000652543	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Dec 15, 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

SCV000652543

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Dec 15, 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 Invitae, SCV000652543.7

#	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 falls in intron 18 of the GFPT1 gene. It does not directly change the encoded amino acid sequence of the GFPT1 protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (no rsID available, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with GFPT1-related conditions. ClinVar contains an entry for this variant (Variation ID: 473132). 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 sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. 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 28, 2024

ClinVar

Relating variation to medicine