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NM_000516.7(GNAS):c.985G>A (p.Gly329Arg) AND not provided

Germline classification:
Uncertain significance (2 submissions)
Last evaluated:
Oct 21, 2021
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:
RCV001585161.7

Allele description [Variation Report for NM_000516.7(GNAS):c.985G>A (p.Gly329Arg)]

NM_000516.7(GNAS):c.985G>A (p.Gly329Arg)

Gene:
GNAS:GNAS complex locus [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
20q13.32
Genomic location:
Preferred name:
NM_000516.7(GNAS):c.985G>A (p.Gly329Arg)
HGVS:
  • NC_000020.11:g.58910348G>A
  • NG_016194.2:g.75609G>A
  • NM_000516.7:c.985G>AMANE SELECT
  • NM_001077488.5:c.988G>A
  • NM_001077489.4:c.940G>A
  • NM_001077490.3:c.*846G>A
  • NM_001309840.2:c.808G>A
  • NM_001309861.2:c.808G>A
  • NM_016592.5:c.*891G>A
  • NM_080425.4:c.2914G>A
  • NM_080426.4:c.943G>A
  • NP_000507.1:p.Gly329Arg
  • NP_001070956.1:p.Gly330Arg
  • NP_001070957.1:p.Gly314Arg
  • NP_001296769.1:p.Gly270Arg
  • NP_001296790.1:p.Gly270Arg
  • NP_536350.2:p.Gly972Arg
  • NP_536351.1:p.Gly315Arg
  • NC_000020.10:g.57485403G>A
  • NM_000516.4:c.985G>A
  • NM_000516.5:c.985G>A
Protein change:
G270R
Links:
dbSNP: rs1394557997
NCBI 1000 Genomes Browser:
rs1394557997
Molecular consequence:
  • NM_001077490.3:c.*846G>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
  • NM_016592.5:c.*891G>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
  • NM_000516.7:c.985G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001077488.5:c.988G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001077489.4:c.940G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001309840.2:c.808G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001309861.2:c.808G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_080425.4:c.2914G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_080426.4:c.943G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:
none provided
Identifiers:
MedGen: C3661900

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001818491GeneDx
criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)		Uncertain significance
(Mar 30, 2020) 		germlineclinical testing

Citation Link,

SCV002317628Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Oct 21, 2021) 		germlineclinical testing

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

Help

Summary from all submissions

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

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From GeneDx, SCV001818491.1

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

Description

In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Not observed in large population cohorts (Lek et al., 2016); Has not been previously published as pathogenic or benign to our knowledge

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

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002317628.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

This sequence change replaces glycine with arginine at codon 329 of the GNAS protein (p.Gly329Arg). The glycine residue is moderately conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is not present in population databases (ExAC no frequency). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals affected with GNAS-related conditions.

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

Last Updated: Oct 13, 2024