NM_017739.4(POMGNT1):c.1539+1G>A AND Myopathy caused by variation in POMGNT1

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Oct 19, 2020
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:: RCV002470740.2

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:: Myopathy caused by variation in POMGNT1
Identifiers:: MONDO: MONDO:0700068; MedGen: CN305639

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002767580	Victorian Clinical Genetics Services, Murdoch Childrens Research Institute See additional submitters Shariant Australia, Australian Genomics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Oct 19, 2020)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 11709191, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002767580

Victorian Clinical Genetics Services, Murdoch Childrens Research Institute

See additional submitters

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Oct 19, 2020)

germline

clinical testing

PubMed (2)
[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	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Muscular dystrophy and neuronal migration disorder caused by mutations in a glycosyltransferase, POMGnT1.

Yoshida A, Kobayashi K, Manya H, Taniguchi K, Kano H, Mizuno M, Inazu T, Mitsuhashi H, Takahashi S, Takeuchi M, Herrmann R, Straub V, Talim B, Voit T, Topaloglu H, Toda T, Endo T.

Dev Cell. 2001 Nov;1(5):717-24.

PubMed [citation]

PMID:: 11709191

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Victorian Clinical Genetics Services, Murdoch Childrens Research Institute, SCV002767580.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

Based on the classification scheme VCGS_Germline_v1.3.3, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with POMGNT-related disorders. (I) 0106 - This gene is associated with autosomal recessive disease. (I) 0209 - Splice site variant proven to affect splicing of the transcript with uncertain effect on protein sequence. RT-RNA analysis has shown this variant causes two aberrant splicing outcomes; a read-through of intronic sequences resulting in a premature stop codon, and exon-skipping leading to an in-frame deletion of 42 amino acids. (PMID: 11709191). (SP) 0251 - This variant is heterozygous. (I) 0304 - Variant is present in gnomAD <0.01 for a recessive condition (v2: 178 heterozygotes, 0 homozygotes). (SP) 0505 - Abnormal splicing is predicted by in silico tools and affected nucleotide is highly conserved. (SP) 0801 - This variant has strong previous evidence of pathogenicity in unrelated individuals with POMGNT1-related disorders (ClinVar; VCGS). (SP) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: May 12, 2024

ClinVar

Relating variation to medicine