Hypogonadotropic hypogonadism
Gene: NSMFComment 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
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.
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.
associated with IHH in the context of other mutated genes (oligogenic inheritance)Created: 24 May 2016, 12:54 p.m.
Mode of inheritance
Other
Gene: nsmf has been classified as Red List (Low Evidence).
Publications for gene: NSMF were set to 15362570; 17235395; 21300340
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
Mode of inheritance for gene: NSMF was changed from BIALLELIC, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
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.
Mode of inheritance for NSMF was changed to BIALLELIC, autosomal or pseudoautosomal
Mode of inheritance for NSMF was changed to Unknown
Mode of inheritance for NSMF was changed to Other - please specifiy in evaluation comments
This gene has been classified as Green List (High Evidence).
This gene has been classified as Green List (High Evidence).
This gene has been classified as Green List (High Evidence).
This gene has been classified as Green List (High Evidence).
Publications for NSMF were set to 15362570; 17235395; 21300340
Publications for NSMF were set to 15362570; 17235395; 21300340
Publications for NSMF were set to 15362570; 17235395
Publications for NSMF were set to 15362570; 17235395
This gene has been classified as Amber List (Moderate Evidence).
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)
NSMF was added to Idiopathic hypogonadotropic hypogonadismpanel. Source: Radboud University Medical Center, Nijmegen
NSMF was added to Idiopathic hypogonadotropic hypogonadismpanel. Source: Emory Genetics Laboratory
NSMF was created by sleigh
NSMF was added to Idiopathic hypogonadotropic hypogonadismpanel. Sources: OMIM