NM_017739.4(POMGNT1):c.964_965del (p.Leu322fs) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Nov 24, 2022
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:: RCV003802829.1

Allele description [Variation Report for NM_017739.4(POMGNT1):c.964_965del (p.Leu322fs)]

NM_017739.4(POMGNT1):c.964_965del (p.Leu322fs)

Genes:

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

Variant type:

Microsatellite

Cytogenetic location:

1p34.1

Genomic location:

Preferred name:

NM_017739.4(POMGNT1):c.964_965del (p.Leu322fs)

HGVS:

NC_000001.11:g.46193625AG[2]
NG_009205.3:g.31676CT[2]
NM_001243766.2:c.964_965del
NM_001290129.2:c.898_899del
NM_001290130.2:c.535_536del
NM_001410783.1:c.964_965del
NM_017739.4:c.964_965delMANE SELECT
NP_001230695.2:p.Leu322fs
NP_001277058.2:p.Leu300fs
NP_001277059.2:p.Leu179fs
NP_001397712.1:p.Leu322fs
NP_060209.4:p.Leu322fs
LRG_701t1:c.964_965del
LRG_701t2:c.964_965del
LRG_701:g.31676CT[2]
LRG_701p1:p.Leu322fs
LRG_701p2:p.Leu322fs
NC_000001.10:g.46659297AG[2]
NC_000001.10:g.46659297_46659298del
NR_024332.1:n.1611_1612CT[2]

Protein change:

L179fs

Molecular consequence:

NM_001243766.2:c.964_965del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001290129.2:c.898_899del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001290130.2:c.535_536del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001410783.1:c.964_965del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_017739.4:c.964_965del - frameshift variant - [Sequence Ontology: SO:0001589]

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
SCV004592886	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 24, 2022)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 19299310, 20816175, 21447391, 26908613, 27391550, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004592886

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 24, 2022)

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

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

POMGnT1, POMT1, and POMT2 mutations in congenital muscular dystrophies.

Endo T, Manya H, Seta N, Guicheney P.

Methods Enzymol. 2010;479:343-52. doi: 10.1016/S0076-6879(10)79019-4.

PubMed [citation]

PMID:: 20816175

See all PubMed Citations (6)

Details of each submission

From Invitae, SCV004592886.1

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

Description

For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This variant has not been reported in the literature in individuals affected with POMGNT1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Leu322Alafs*16) in the POMGNT1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in POMGNT1 are known to be pathogenic (PMID: 19299310, 20816175, 21447391, 26908613, 27391550).

#	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: Mar 5, 2024

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