NM_017739.4(POMGNT1):c.1895+1G>T AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 28, 2024
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:: RCV000704718.13

Allele description [Variation Report for NM_017739.4(POMGNT1):c.1895+1G>T]

NM_017739.4(POMGNT1):c.1895+1G>T

Genes:

POMGNT1:protein O-linked mannose N-acetylglucosaminyltransferase 1 (beta 1,2-) [Gene - OMIM - HGNC]
TSPAN1:tetraspanin 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1p34.1

Genomic location:

Preferred name:

NM_017739.4(POMGNT1):c.1895+1G>T

HGVS:

NC_000001.11:g.46189457C>A
NG_009205.3:g.35849G>T
NM_001243766.2:c.1869+27G>T
NM_001290129.2:c.1829+1G>T
NM_001290130.2:c.1466+1G>T
NM_001410783.1:c.1895+1G>T
NM_017739.4:c.1895+1G>TMANE SELECT
LRG_701t1:c.1869+27G>T
LRG_701t2:c.1895+1G>T
LRG_701:g.35849G>T
NC_000001.10:g.46655129C>A
NM_001290129.1:c.1829+1G>T
NM_017739.3:c.1895+1G>T

Links:

dbSNP: rs386834024

NCBI 1000 Genomes Browser:

rs386834024

Molecular consequence:

NM_001243766.2:c.1869+27G>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001290129.2:c.1829+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001290130.2:c.1466+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001410783.1:c.1895+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
NM_017739.4:c.1895+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Name:: Autosomal recessive limb-girdle muscular dystrophy type 2O
Synonyms:: MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (LIMB-GIRDLE), TYPE C, 3; MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY, LIMB-GIRDLE, POMGNT1-RELATED; Limb-Girdle Muscular Dystrophy Type 3C; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0013161; MedGen: C3150417; Orphanet: 206564; OMIM: 613157

Name:: Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B3 (MDDGB3)
Synonyms:: MUSCULAR DYSTROPHY, CONGENITAL, POMGNT1-RELATED; MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (CONGENITAL WITH IMPAIRED INTELLECTUAL DEVELOPMENT), TYPE B, 3
Identifiers:: MONDO: MONDO:0013155; MedGen: C3150412; OMIM: 613151

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000833678	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 28, 2024)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 15466003, 22554691, 17576681, 9536098, 28424332, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000833678

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 28, 2024)

germline

clinical testing

PubMed (6)
[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

POMGnT1 mutation and phenotypic spectrum in muscle-eye-brain disease.

Diesen C, Saarinen A, Pihko H, Rosenlew C, Cormand B, Dobyns WB, Dieguez J, Valanne L, Joensuu T, Lehesjoki AE.

J Med Genet. 2004 Oct;41(10):e115. No abstract available.

PubMed [citation]

PMID:: 15466003
PMCID:: PMC1735594

Novel POMGNT1 point mutations and intragenic rearrangements associated with muscle-eye-brain disease.

Saredi S, Ardissone A, Ruggieri A, Mottarelli E, Farina L, Rinaldi R, Silvestri E, Gandioli C, D'Arrigo S, Salerno F, Morandi L, Grammatico P, Pantaleoni C, Moroni I, Mora M.

J Neurol Sci. 2012 Jul 15;318(1-2):45-50. doi: 10.1016/j.jns.2012.04.008. Epub 2012 May 2.

PubMed [citation]

PMID:: 22554691
PMCID:: PMC3405532

See all PubMed Citations (6)

Details of each submission

From Invitae, SCV000833678.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

This sequence change affects a donor splice site in intron 21 of the POMGNT1 gene. RNA analysis indicates that disruption of this splice site induces altered splicing and likely disrupts the C-terminus of the protein. This variant is present in population databases (rs386834024, gnomAD 0.02%). Disruption of this splice site has been observed in individual(s) with muscular dystrophy-dystroglycanopathy (PMID: 15466003, 22554691, 28424332). 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: 56593). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that disruption of this splice site results in partial inclusion of intron 21 (also known as intron 25) and introduces a new termination codon (PMID: 28424332). However the mRNA is not expected to undergo nonsense-mediated decay. For these reasons, this variant has been classified as Pathogenic.

#	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 8, 2024

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