Hypogonadotropic hypogonadism

Gene: NSMF

Green List (high evidence)

NSMF (NMDA receptor synaptonuclear signaling and neuronal migration factor)
EnsemblGeneIds (GRCh38): ENSG00000165802
EnsemblGeneIds (GRCh37): ENSG00000165802
OMIM: 608137, Gene2Phenotype
NSMF is in 3 panels

5 reviews

Mehul Dattani (UCL Institute of Child Health)

Green List (high evidence)

Louise IZATT (GSTT Clinical Genetics Service)

Green List (high evidence)

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 publications
Created: 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)

Green List (high evidence)

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
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Radboud University Medical Center, Nijmegen
  • Emory Genetics Laboratory
  • OMIM
Phenotypes
  • Hypogonadotropic hypogonadism 9 with or without anosmia, 614838
  • Endocrine Disorders including conditions such as hypogonadotropic hypogonadism (with or without anosmia): Sequencing Panel (Emory)
Tags
monogenic-polygenic
OMIM
608137
Clinvar variants
Variants in NSMF
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

28 Oct 2016, Gel status: 4

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.

28 Oct 2016, Gel status: 4

Set Mode of Inheritance

Ellen McDonagh (Genomics England Curator)

Mode of inheritance for NSMF was changed to BIALLELIC, autosomal or pseudoautosomal

14 Oct 2016, Gel status: 4

Set Mode of Inheritance

Sarah Leigh (Genomics England Curator)

Mode of inheritance for NSMF was changed to Unknown

18 Jul 2016, Gel status: 4

Set Mode of Inheritance

Ellen McDonagh (Genomics England Curator)

Mode of inheritance for NSMF was changed to Other - please specifiy in evaluation comments

1 Jun 2016, Gel status: 4

Gene classified by Genomics England curator

Sarah Leigh (Genomics England Curator)

This gene has been classified as Green List (High Evidence).

1 Jun 2016, Gel status: 4

Gene classified by Genomics England curator

Sarah Leigh (Genomics England Curator)

This gene has been classified as Green List (High Evidence).

1 Jun 2016, Gel status: 4

Gene classified by Genomics England curator

Sarah Leigh (Genomics England Curator)

This gene has been classified as Green List (High Evidence).

1 Jun 2016, Gel status: 4

Gene classified by Genomics England curator

Sarah Leigh (Genomics England Curator)

This gene has been classified as Green List (High Evidence).

1 Jun 2016, Gel status: 2

Set publications

Sarah Leigh (Genomics England Curator)

Publications for NSMF were set to 15362570; 17235395; 21300340

1 Jun 2016, Gel status: 2

Set publications

Sarah Leigh (Genomics England Curator)

Publications for NSMF were set to 15362570; 17235395; 21300340

1 Jun 2016, Gel status: 2

Set publications

Sarah Leigh (Genomics England Curator)

Publications for NSMF were set to 15362570; 17235395

27 May 2016, Gel status: 2

Set publications

Sarah Leigh (Genomics England Curator)

Publications for NSMF were set to 15362570; 17235395

26 May 2016, Gel status: 2

Gene classified by Genomics England curator

Sarah Leigh (Genomics England Curator)

This gene has been classified as Amber List (Moderate Evidence).

26 May 2016, Gel status: 2

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)

17 May 2016, Gel status: 2

Added New Source

Sarah Leigh (Genomics England Curator)

NSMF was added to Idiopathic hypogonadotropic hypogonadismpanel. Source: Radboud University Medical Center, Nijmegen

17 May 2016, Gel status: 1

Added New Source

Sarah Leigh (Genomics England Curator)

NSMF was added to Idiopathic hypogonadotropic hypogonadismpanel. Source: Emory Genetics Laboratory

17 May 2016, Gel status: 0

Added New Source

Sarah Leigh (Genomics England Curator)

NSMF was added to Idiopathic hypogonadotropic hypogonadismpanel. Sources: OMIM

17 May 2016, Gel status: 0

Created

Sarah Leigh (Genomics England Curator)

NSMF was created by sleigh