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NM_000406.3(GNRHR):c.436C>T (p.Pro146Ser) AND GNRHR-related disorder

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Feb 27, 2024
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:
RCV003935381.1

Allele description [Variation Report for NM_000406.3(GNRHR):c.436C>T (p.Pro146Ser)]

NM_000406.3(GNRHR):c.436C>T (p.Pro146Ser)

Gene:
GNRHR:gonadotropin releasing hormone receptor [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
4q13.2
Genomic location:
Preferred name:
NM_000406.3(GNRHR):c.436C>T (p.Pro146Ser)
HGVS:
  • NC_000004.12:g.67753900G>A
  • NG_009293.1:g.7187C>T
  • NM_000406.3:c.436C>TMANE SELECT
  • NM_001012763.2:c.436C>T
  • NP_000397.1:p.Pro146Ser
  • NP_000397.1:p.Pro146Ser
  • NP_001012781.1:p.Pro146Ser
  • NC_000004.11:g.68619618G>A
  • NM_000406.2:c.436C>T
Protein change:
P146S
Links:
dbSNP: rs144900788
NCBI 1000 Genomes Browser:
rs144900788
Molecular consequence:
  • NM_000406.3:c.436C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001012763.2:c.436C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
GNRHR-related disorder
Synonyms:
GNRHR-related condition
Identifiers:

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004754554PreventionGenetics, part of Exact Sciences
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain significance
(Feb 27, 2024) 		germlineclinical testing

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

Help

Summary from all submissions

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

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 PreventionGenetics, part of Exact Sciences, SCV004754554.1

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

Description

The GNRHR c.436C>T variant is predicted to result in the amino acid substitution p.Pro146Ser. This variant has been reported in the heterozygous state in several patients with hypogonadotropic hypogonadism/Kallmann syndrome (see, for example, Vagenakis et al. 2005. PubMed ID: 16359986; Gianetti et al. 2012. PubMed ID: 22745237; Miraoui et al. 2013. PubMed ID: 23643382, Table S3; Stamou et al. 2019. PubMed ID: 30921766), delayed puberty (Saengkaew et al. 2021. PubMed ID: 34403359), or a suspected disorder of sex development (Zidoune et al. 2022. PubMed ID: 36110220, supplementary data). However, a second pathogenic variant was not identified in these patients. In addition, no genetic or functional study has been performed to assess the pathogenicity of this variant. This variant has been observed with an allele frequency of up to ~0.38% in Latino individuals from a large population database, including 1 homozygote. At this time, the clinical significance of this 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: May 12, 2024