NM_017739.4(POMGNT1):c.1463G>A (p.Arg488Gln) AND Muscular dystrophy-dystroglycanopathy

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Jan 24, 2023
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:
RCV002525910.2

Allele description [Variation Report for NM_017739.4(POMGNT1):c.1463G>A (p.Arg488Gln)]

NM_017739.4(POMGNT1):c.1463G>A (p.Arg488Gln)

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.1463G>A (p.Arg488Gln)
Other names:
NM_017739.4(POMGNT1):c.1463G>A; p.Arg488Gln
HGVS:
  • NC_000001.11:g.46192174C>T
  • NG_009205.3:g.33132G>A
  • NM_001243766.2:c.1463G>A
  • NM_001290129.2:c.1397G>A
  • NM_001290130.2:c.1034G>A
  • NM_017739.4:c.1463G>AMANE SELECT
  • NP_001230695.2:p.Arg488Gln
  • NP_001277058.2:p.Arg466Gln
  • NP_001277059.2:p.Arg345Gln
  • NP_060209.3:p.Arg488Gln
  • NP_060209.4:p.Arg488Gln
  • LRG_701t1:c.1463G>A
  • LRG_701t2:c.1463G>A
  • LRG_701:g.33132G>A
  • LRG_701p1:p.Arg488Gln
  • LRG_701p2:p.Arg488Gln
  • NC_000001.10:g.46657846C>T
  • NG_009205.2:g.33132G>A
  • NM_017739.3:c.1463G>A
Protein change:
R345Q
Links:
dbSNP: rs766382416
NCBI 1000 Genomes Browser:
rs766382416
Molecular consequence:
  • NM_001243766.2:c.1463G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001290129.2:c.1397G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001290130.2:c.1034G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_017739.4:c.1463G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Muscular dystrophy-dystroglycanopathy
Synonyms:
Congenital muscular dystrophy due to dystroglycanopathy
Identifiers:
MONDO: MONDO:0018276; MedGen: C5679911; Orphanet: 370953

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV003761163Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain significance
(Jan 24, 2023) 		germlinecuration

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedcuration

Citations

PubMed

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 Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard, SCV003761163.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcuration PubMed (1)

Description

The p.Arg488Gln variant in POMGNT1 has not been previously reported in the literature in individuals with POMGNT1-associated muscular dystrophy-dystroglycanopathy, but has been identified in 0.004% (5/113768) of European (non-Finnish) chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP ID: rs766382416). Although this variant has been seen in the general population in a heterozygous state, its frequency is low enough to be consistent with a recessive carrier frequency. This variant has also been reported in ClinVar (Variation ID#:422459) as likely pathogenic by GeneDx and as a variant of uncertain significance by Counsyl and Invitae. Computational prediction tools and conservation analyses suggest that this variant may impact the protein, though this information is not predictive enough to determine pathogenicity. In summary, the clinical significance of the p.Arg488Gln variant is uncertain. ACMG/AMP Criteria applied: PM2_Supporting, PP3 (Richards 2015).

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024