Hypogonadotropic hypogonadism
Gene: NSMFEnsemblGeneIds (GRCh38): ENSG00000165802
EnsemblGeneIds (GRCh37): ENSG00000165802
OMIM: 608137, Gene2Phenotype
NSMF is in 3 panels
6 reviews
Arina Puzriakova (Genomics England Curator)
Comment on list classification: Downgrading from Green to Red to align with the classification on the GMS equivalent panel (https://panelapp.genomicsengland.co.uk/panels/650/gene/NSMF/)
Review by Zornitza Stark (Australian Genomics) - 18 Jul 2020
"Rare variants reported in individuals with IHH; however, variants in other IHH genes also present, and at least one of the variants has a very high population frequency in gnomad (intronic 8-bp deletion ending 14 bp before exon 10 (1159-14_-22del), present in 258 individuals)."
Review by Ivone Leong (Genomics England Curator) - 24 Mar 2021
"This gene is associated with a phenotype in OMIM but not in Gene2Phenotype. PMID:27803842 describes a murine Nsmf knockout model that shows that Nsmf does not have a role in the migration of GnRH-positive neurons during early development.
Given the available evidence, this gene should be demoted to Red status."Created: 30 Nov 2023, 12:08 p.m. | Last Modified: 30 Nov 2023, 12:08 p.m.
Panel Version: 1.40
Comment on mode of inheritance: Updated from biallelic to monoallelic as only heterozygous variants in this gene have been reported in association with IHH, even though this only partially explains the phenotype in some cases due to oligogenic variants in other genes such as FGFR1 and HS6ST1.Created: 30 Nov 2023, 12:05 p.m. | Last Modified: 30 Nov 2023, 12:08 p.m.
Panel Version: 1.40
Mehul Dattani (UCL Institute of Child Health)
Louise IZATT (GSTT Clinical Genetics Service)
Ellen McDonagh (Genomics England Curator)
Comment on mode of inheritance: Changed the mode of inheritance from 'Both' to 'Biallelic', before promoting this panel to version 1 due to internal discussion. It may be that studies reporting monoallelic variants in this gene did not examine fully whether variants in other genes had a second variant and therefore monoallelic variants in this gene may not provide a complete diagnosis.Created: 28 Oct 2016, 1:21 p.m.
Sarah Leigh (Genomics England Curator)
Comment on list classification: One Htz NSMF variant reported, two as compound Htz and three digenic with pathogenic FGFR1, KAL1 and TACR3 variants. See comments for publicationsCreated: 1 Jun 2016, 9:48 a.m.
Comment on publications: PMID 15362570: Report of Htz variant c.1438A>G, p.(T480A) rs121918340 low evidence for pathogenicity (no in vitro & low in silico). PMID 17235395: Report of NSMF c.1132-23_1132-15delTTGTGGCCT (rs606231136) in vitro evidence that deletion causes skipping of NSMF exon 10, this variant is digenic with FGFR1 variant p.(L342S). PMID 21300340: Compound Htz c.629-21G>C / c.629-23C>G, 50% reduced peptide, mRNA level and length normal. c.757G>A, p.Ala253Thr (rs142726563), 50% reduced peptide, mRNA level and length normal, digenic with c.488_490delGTT p.Cys163del of KAL1. c.1160-13C>T, in vitro evidence for skipping of exon 10 resulting in frameshift and termination, digenic with c.824G>A, p.(Trp275*) of TACR3.Created: 1 Jun 2016, 9:41 a.m.
Richard Quinton (Newcastle University)
associated with IHH in the context of other mutated genes (oligogenic inheritance)Created: 24 May 2016, 12:54 p.m.
Mode of inheritance
Other
Details
- Mode of Inheritance
- MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
- Sources
-
- Expert Review Red
- Radboud University Medical Center, Nijmegen
- Emory Genetics Laboratory
- OMIM
- Phenotypes
-
- Hypogonadotropic hypogonadism 9 with or without anosmia, OMIM:614838
- Tags
- OMIM
- 608137
- Clinvar variants
- Variants in NSMF
- Penetrance
- Complete
- Publications
- Panels with this gene
History Filter Activity
Entity classified by Genomics England curator
Arina Puzriakova (Genomics England Curator)Gene: nsmf has been classified as Red List (Low Evidence).
Set publications
Arina Puzriakova (Genomics England Curator)Publications for gene: NSMF were set to 15362570; 17235395; 21300340
Set Phenotypes
Arina Puzriakova (Genomics England Curator)Phenotypes for gene: NSMF were changed from Hypogonadotropic hypogonadism 9 with or without anosmia, 614838; Endocrine Disorders including conditions such as hypogonadotropic hypogonadism (with or without anosmia): Sequencing Panel (Emory) to Hypogonadotropic hypogonadism 9 with or without anosmia, OMIM:614838
Set mode of inheritance
Arina Puzriakova (Genomics England Curator)Mode of inheritance for gene: NSMF was changed from BIALLELIC, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
panel promoted to version 1
Ellen McDonagh (Genomics England Curator)28th Oct 2016: This panel was revised after external expert review and internal discussion. For several genes that have been shown to contribute to the disorder in a digenic/polygenic manner, the decision was made to only include genes as green if biallelic variants had been reported independently from other genes. Genes with a monoallelic mechanism, that have been shown in some studies in conjunction with variants in other genes, were made red as monoallelic variants in these genes may not provide a complete diagnosis.
Set Mode of Inheritance
Ellen McDonagh (Genomics England Curator)Mode of inheritance for NSMF was changed to BIALLELIC, autosomal or pseudoautosomal
Set Mode of Inheritance
Sarah Leigh (Genomics England Curator)Mode of inheritance for NSMF was changed to Unknown
Set Mode of Inheritance
Ellen McDonagh (Genomics England Curator)Mode of inheritance for NSMF was changed to Other - please specifiy in evaluation comments
Gene classified by Genomics England curator
Sarah Leigh (Genomics England Curator)This gene has been classified as Green List (High Evidence).
Gene classified by Genomics England curator
Sarah Leigh (Genomics England Curator)This gene has been classified as Green List (High Evidence).
Gene classified by Genomics England curator
Sarah Leigh (Genomics England Curator)This gene has been classified as Green List (High Evidence).
Gene classified by Genomics England curator
Sarah Leigh (Genomics England Curator)This gene has been classified as Green List (High Evidence).
Set publications
Sarah Leigh (Genomics England Curator)Publications for NSMF were set to 15362570; 17235395; 21300340
Set publications
Sarah Leigh (Genomics England Curator)Publications for NSMF were set to 15362570; 17235395; 21300340
Set publications
Sarah Leigh (Genomics England Curator)Publications for NSMF were set to 15362570; 17235395
Set publications
Sarah Leigh (Genomics England Curator)Publications for NSMF were set to 15362570; 17235395
Gene classified by Genomics England curator
Sarah Leigh (Genomics England Curator)This gene has been classified as Amber List (Moderate Evidence).
Set Phenotypes
Sarah Leigh (Genomics England Curator)Phenotypes for gene NSMF were set to Hypogonadotropic hypogonadism 9 with or without anosmia, 614838;Endocrine Disorders including conditions such as hypogonadotropic hypogonadism (with or without anosmia): Sequencing Panel (Emory)
Added New Source
Sarah Leigh (Genomics England Curator)NSMF was added to Idiopathic hypogonadotropic hypogonadismpanel. Source: Radboud University Medical Center, Nijmegen
Added New Source
Sarah Leigh (Genomics England Curator)NSMF was added to Idiopathic hypogonadotropic hypogonadismpanel. Source: Emory Genetics Laboratory
Created
Sarah Leigh (Genomics England Curator)NSMF was created by sleigh
Added New Source
Sarah Leigh (Genomics England Curator)NSMF was added to Idiopathic hypogonadotropic hypogonadismpanel. Sources: OMIM