NM_017739.4(POMGNT1):c.1895+1G>T AND POMGNT1-related disorder

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Feb 14, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000778243.12

Allele description

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:: POMGNT1-related disorder
Synonyms:: POMGNT1-Related Disorders; POMGNT1-related condition
Identifiers:: MedGen: CN239299

Recent activity

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Cochleoceps bassensis voucher NMV A 8875 SH3 and PX domain-containing 3 protein ...
Cochleoceps bassensis voucher NMV A 8875 SH3 and PX domain-containing 3 protein (sh3px3) gene, partial cds
gi|2033086409|gb|MT569783.1|

Nucleotide
(GDS2775[ACCN]) AND GDS[filter] (1)
GDSBrowser
Nuclear factor I-A deficiency effect on brain development
Nuclear factor I-A deficiency effect on brain development
Accession: GDS2775

GDSBrowser
Mus musculus cDNA sequence BC020535, mRNA (cDNA clone MGC:19360 IMAGE:4240594), ...
Mus musculus cDNA sequence BC020535, mRNA (cDNA clone MGC:19360 IMAGE:4240594), complete cds
gi|18088218|gb|BC020535.1|

Nucleotide
AV700541 GKC Homo sapiens cDNA clone GKCADH01 3', mRNA sequence
AV700541 GKC Homo sapiens cDNA clone GKCADH01 3', mRNA sequence
gi|10302512|gnl|dbEST|6140031|dbj|A 41.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000914412	Illumina Laboratory Services, Illumina	criteria provided, single submitter (ICSL Variant Classification Criteria 09 May 2019)	Pathogenic (May 3, 2018)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 22323514, 19299310, 15466003, 22554691 Citation Link,
SCV004741883	PreventionGenetics, part of Exact Sciences	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Feb 14, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000914412

Illumina Laboratory Services, Illumina

criteria provided, single submitter

(ICSL Variant Classification Criteria 09 May 2019)

Pathogenic
(May 3, 2018)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

Citation Link,

SCV004741883

PreventionGenetics, part of Exact Sciences

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Feb 14, 2024)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

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

Cobblestone lissencephaly: neuropathological subtypes and correlations with genes of dystroglycanopathies.

Devisme L, Bouchet C, Gonzalès M, Alanio E, Bazin A, Bessières B, Bigi N, Blanchet P, Bonneau D, Bonnières M, Bucourt M, Carles D, Clarisse B, Delahaye S, Fallet-Bianco C, Figarella-Branger D, Gaillard D, Gasser B, Delezoide AL, Guimiot F, Joubert M, Laurent N, et al.

Brain. 2012 Feb;135(Pt 2):469-82. doi: 10.1093/brain/awr357. Epub 2012 Feb 9.

PubMed [citation]

PMID:: 22323514

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. doi: 10.1212/WNL.0000000000007479.

PubMed [citation]

PMID:: 19299310

See all PubMed Citations (5)

Details of each submission

From Illumina Laboratory Services, Illumina, SCV000914412.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

The POMGNT1 c.1895+1G>T variant occurs in a canonical splice site (donor) and is therefore predicted to disrupt or distort the normal gene product. The variant has been reported in at least four studies in which it is found in a compound heterozygous state in three individuals with muscle-eye-brain disease and in one individual with cobblestone lissencephaly (Diesen et al. 2004; Mercuri et al. 2009; Saredi et al. 2012; Devisme et al. 2012). The variant was absent from at least 125 control individuals and is reported at a frequency of 0.00047 in the European (non-Finnish) population of the Exome Aggregation Consortium. RT-PCR experiments demonstrated that the variant affects splicing with retention of the intron between exons 21 and 22 (Saredi et al. 2012). Due to the potential impact of splice donor variants and the evidence from the literature, the c.1895+1G>T variant is classified as pathogenic for POMGNT1-related disorders. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.

#	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

From PreventionGenetics, part of Exact Sciences, SCV004741883.1

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

Description

The POMGNT1 c.1895+1G>T variant is predicted to disrupt the GT donor site and interfere with normal splicing. This variant has been reported in several unrelated individuals with muscle-eye-brain disease (see for example, Saredi et al. 2012. PubMed ID: 22554691; Diesen et al. 2004. PubMed ID: 15466003). Functional RNA studies on this variant have shown it leads to retention of intron 21 (Saredi et al. 2012. PubMed ID: 22554691). This variant is reported in 0.020% of alleles in individuals of European (Finnish) descent in gnomAD. Variants that disrupt the consensus splice donor site in POMGNT1 are expected to be pathogenic. This variant is interpreted 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 29, 2024

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