NM_017739.4(POMGNT1):c.1539+1G>A AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 29, 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:: RCV000648199.9

Allele description [Variation Report for NM_017739.4(POMGNT1):c.1539+1G>A]

NM_017739.4(POMGNT1):c.1539+1G>A

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.1539+1G>A

HGVS:

NC_000001.11:g.46192097C>T
NG_009205.3:g.33209G>A
NM_001243766.2:c.1539+1G>A
NM_001290129.2:c.1473+1G>A
NM_001290130.2:c.1110+1G>A
NM_001410783.1:c.1539+1G>A
NM_017739.4:c.1539+1G>AMANE SELECT
LRG_701t1:c.1539+1G>A
LRG_701t2:c.1539+1G>A
LRG_701:g.33209G>A
NC_000001.10:g.46657769C>T
NM_001243766.1:c.1539+1G>A
NM_017739.3:c.1539+1G>A

Note:

Until November, 2022 the allelic variant 606822.0002 was erroneously defined as NM_017739.4(POMGNT1):c.1413+1G>A.

Nucleotide change:

IVS17DS, G-A, +1

Links:

OMIM: 606822.0002; dbSNP: rs138642840

NCBI 1000 Genomes Browser:

rs138642840

Molecular consequence:

NM_001243766.2:c.1539+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001290129.2:c.1473+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001290130.2:c.1110+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001410783.1:c.1539+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_017739.4:c.1539+1G>A - 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

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
SCV000770013	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 29, 2024)	germline	clinical testing	PubMed (9) [See all records that cite these PMIDs] 16199547, 19299310, 20816175, 21447391, 26908613, 27391550, 11709191, 23326386, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000770013

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 29, 2024)

germline

clinical testing

PubMed (9)
[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

Splicing in action: assessing disease causing sequence changes.

Baralle D, Baralle M.

J Med Genet. 2005 Oct;42(10):737-48. Review.

PubMed [citation]

PMID:: 16199547
PMCID:: PMC1735933

Congenital muscular dystrophies with defective glycosylation of dystroglycan: a population study.

Mercuri E, Messina S, Bruno C, Mora M, Pegoraro E, Comi GP, D'Amico A, Aiello C, Biancheri R, Berardinelli A, Boffi P, Cassandrini D, Laverda A, Moggio M, Morandi L, Moroni I, Pane M, Pezzani R, Pichiecchio A, Pini A, Minetti C, Mongini T, et al.

Neurology. 2009 May 26;72(21):1802-9. doi: 10.1212/01.wnl.0000346518.68110.60. Epub 2009 Mar 18. Erratum in: Neurology. 2019 Aug 20;93(8):371.

PubMed [citation]

PMID:: 19299310

See all PubMed Citations (9)

Details of each submission

From Invitae, SCV000770013.7

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (9)

Description

This sequence change affects a donor splice site in intron 17 of the POMGNT1 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in POMGNT1 are known to be pathogenic (PMID: 19299310, 20816175, 21447391, 26908613, 27391550). This variant is present in population databases (rs138642840, gnomAD 0.2%), and has an allele count higher than expected for a pathogenic variant. Disruption of this splice site has been observed in individuals with muscle-eye-brain disease and congenital muscular dystrophy (PMID: 11709191, 23326386). This variant is also known as IVS17+1G>A. ClinVar contains an entry for this variant (Variation ID: 56582). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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: May 12, 2024

ClinVar

Relating variation to medicine