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NM_016592.5(GNAS):c.505C>T (p.Arg169Ter) AND GNAS-related disorder

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Feb 20, 2024
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
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:
RCV004542355.2

Allele description [Variation Report for NM_016592.5(GNAS):c.505C>T (p.Arg169Ter)]

NM_016592.5(GNAS):c.505C>T (p.Arg169Ter)

Genes:
GNAS-AS1:GNAS antisense RNA 1 [Gene - OMIM - HGNC]
GNAS:GNAS complex locus [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
20q13.32
Genomic location:
Preferred name:
NM_016592.5(GNAS):c.505C>T (p.Arg169Ter)
HGVS:
  • NC_000020.11:g.58840611C>T
  • NG_016194.2:g.5872C>T
  • NG_021433.1:g.15293G>A
  • NM_001410912.1:c.-233C>T
  • NM_016592.5:c.505C>T
  • NP_057676.1:p.Arg169Ter
  • LRG_1051:g.15293G>A
  • NC_000020.10:g.57415666C>T
  • NM_016592.3:c.505C>T
Protein change:
R169*
Molecular consequence:
  • NM_001410912.1:c.-233C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_016592.5:c.505C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:
GNAS-related disorder
Identifiers:

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004761637PreventionGenetics, part of Exact Sciences
no assertion criteria provided
Uncertain significance
(Feb 20, 2024) 		germlineclinical testing

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Details of each submission

From PreventionGenetics, part of Exact Sciences, SCV004761637.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The GNAS c.505C>T variant is predicted to result in premature protein termination (p.Arg169*). To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.020% of alleles in individuals of Latino descent in gnomAD. Transcript NM_016592.3 only has one coding exon and encodes neuroendocrine secretory protein 55 (NESP55). This exon is located ~51kb upstream of the first exon of the primary transcript (NM_000516.5) of GNAS. To our knowledge, only large deletions of this region are conclusively pathogenic for pseudohypoparathyroidism type-Ib (PHP-Ib) due to methylation defects, of which obesity is not typically characteristic feature (Turan and Bastepe. 2015. PubMed ID: 25851935). Although, in some studies single nucleotide variants (SNVs) within this region have been reported in related diseases, the pathogenicity is still unknown (see for example in Table 3 of Long et al. 2018. PubMed ID: 30022773). Taken together, at this time, the clinical significance of this nonsense variant is uncertain due to the absence of conclusive functional and genetic evidence.

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

Last Updated: Nov 3, 2024