NM_000406.3(GNRHR):c.941T>A (p.Leu314Ter) AND Hypogonadotropic hypogonadism 7 with or without anosmia

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Feb 18, 2022
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:: RCV000030913.30

Allele description [Variation Report for NM_000406.3(GNRHR):c.941T>A (p.Leu314Ter)]

NM_000406.3(GNRHR):c.941T>A (p.Leu314Ter)

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.941T>A (p.Leu314Ter)

HGVS:

NC_000004.12:g.67740526A>T
NG_009293.1:g.20561T>A
NM_000406.3:c.941T>AMANE SELECT
NM_001012763.2:c.*63T>A
NP_000397.1:p.Leu314Ter
NC_000004.11:g.68606244A>T

Protein change:

L314*; LEU314TER

Links:

OMIM: 138850.0007; dbSNP: rs104893841

NCBI 1000 Genomes Browser:

rs104893841

Molecular consequence:

NM_001012763.2:c.*63T>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_000406.3:c.941T>A - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Hypogonadotropic hypogonadism 7 with or without anosmia (HH7)
Synonyms:: HYPOGONADOTROPIC HYPOGONADISM 7 WITHOUT ANOSMIA
Identifiers:: MONDO: MONDO:0007794; MedGen: C0342384; Orphanet: 432; OMIM: 146110

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000037676	OMIM	no assertion criteria provided	Pathogenic (Feb 18, 2022)	germline	literature only	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000037676

OMIM

no assertion criteria provided

Pathogenic
(Feb 18, 2022)

germline

literature only

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

Subregional mapping of the human gonadotropin-releasing hormone receptor (GnRH-R) gene to 4q between the markers D4S392 and D4S409.

Kottler ML, Lorenzo F, Bergametti F, Commerçon P, Souchier C, Counis R.

Hum Genet. 1995 Oct;96(4):477-80.

PubMed [citation]

PMID:: 7557974

Details of each submission

From OMIM, SCV000037676.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

Description

In a woman with complete hypogonadotropic hypogonadism (HH7; 146110), Kottler et al. (2000) identified compound heterozygosity for 2 mutations in the GNRHR gene: the Q106R mutation (138850.0001) and a leu314-to-ter (L314X) substitution, resulting in partial deletion of the seventh transmembrane domain. The L314X mutant receptor showed neither measurable binding nor inositol phosphate production when transfected in CHO-K1 cells compared to the wildtype receptor. Family members who were heterozygous for either mutation had normal pubertal development and fertility.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Apr 23, 2022

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