Disorders of sex development

Gene: TSPYL1

Amber List (moderate evidence)

TSPYL1 (TSPY like 1)
EnsemblGeneIds (GRCh38): ENSG00000189241
EnsemblGeneIds (GRCh37): ENSG00000189241
OMIM: 604714, Gene2Phenotype
TSPYL1 is in 3 panels

5 reviews

Eleanor Williams (Genomics England Curator)

Green List (high evidence)

Comment on list classification: Leaving rating as amber, but there are 3 cases now reported and so this gene should be reviewed at the next GMS update.
Created: 11 Jan 2021, 10:14 p.m. | Last Modified: 11 Jan 2021, 10:14 p.m.
Panel Version: 2.14
2 additional independent cases with the same biallelic variant in TSPYL1 in patients with Sudden Infant Death with Dysgenesis of the Testes syndrome reported. This, along with case reported by Puffenberger et al 2004 (PMID: 15273283) brings the total to 3.

PMID: 32885560 - Slater et al 2020 - report a Hispanic, phenotypically female infant with poor feeding and abnormal motor movements noted at birth. Mild T-cell lymphopenia, absent uterus and adnexal structures, with no gonads visible and intractable epilepsy are also reported. The patient died of respiratory failure at 8 months of age. Exome sequencing revealed homozygosity for a frameshift variant in TSPYL1 (c.725_726delTG, p.Val242GlufsTer52). The variant has a frequency of 0.002% in gnomAD but has not been reported in the homozygous state.

PMID: 33075815 - Buyse et al 2020 - report 3 affected siblings from a consanguineous Turkish family. The phenotype was characterized by visceroautonomic dysfunction, severe postnatal progressive neurological abnormalities, visual impairment, testicular dysgenesis in males and sudden death at infant age. WES analysis found a homozygous frameshift variant p.Val242GlufsTer52 in TSPYL1 in the affected siblings. The variant is found in gnomAD at a MAF of 0.0021%, but no homozygous individuals are reported. The parents and one unaffected sibling were heterozygous for the variant. The truncated protein was retained in the Golgi in patient fibroblasts whereas in control fibroblasts the full length protein was found in the nucleus. Patient cells also showed prolonged S and G2 phases with reduced cellular proliferation rates. Tspyl1 depleted zebrafish showed a similar phenotype with early lethality, defects in neurogenesis and cardiac dilation.
Created: 11 Jan 2021, 10:12 p.m. | Last Modified: 11 Jan 2021, 10:12 p.m.
Panel Version: 2.11

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Sudden infant death with dysgenesis of the testes syndrome OMIM:608800; sudden infant death-dysgenesis of the testes syndrome MONDO:0012124

Publications

Ivone Leong (Genomics England Curator)

Comment on list classification: Promoted from red to amber. TSPYL1 is associated with a phenotype in OMIM but not Gene2Phenotype. As there are only 2 unrelated cases with different variants in the gene, it was decided that there is currently not enough evidence to promote to green status. There was agreement to promote this gene to amber by experts in GMS Endocrinology Specialist Test Group. Until further evidence is available, TSPYL1 will be promoted to amber.
Created: 8 May 2019, 9:31 a.m.

Stephanie Allen (Consultant Clinical Scientist)

Green List (high evidence)

Additional case detected by DSD panel (routine diagnostic testing). Apparent homozygote for nonsense variant in TSPYL1 close to that published in Puffenberger paper (array CGH - deletion on other allele). Neonatal presentation. No further information, not published yet. Strong evidence when viewed in combination with large Amish family in Puffenberger paper (segregation). Likely to be rare cause, but upgraded to green.
Created: 4 Mar 2019, 1:48 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Mode of pathogenicity
Other

Sarah Leigh (Genomics England Curator)

Comment when marking as ready: Associated with phenotype in OMIM, not in G2P / DD. One homozygous variant reported in large family with phenotype of Sudden infant death with dysgenesis of the testes syndrome 608800. Additionally four heterozygous variants reported in one case of 46,XY disorder of sex development with male infertility and one case of 46,XY female with complete gonadal dysgenesis (PMID 19463995) and two cases of male idiopathic infertility (PMID 22137496). However, the pathogenicity of these variants is as yet uncertain
Created: 3 Nov 2016, 11:19 a.m.

John Achermann (UCL Institute of Child Health)

Red List (low evidence)

Single large pedigree reported with 46,XY testicular dysgenesis and sudden infant death.
Created: 4 Feb 2016, 4:58 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
sudden infant death and testicular dysgenesis

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Amber
  • Other
  • Radboud University Medical Center, Nijmegen
  • Expert list
Phenotypes
  • Sudden infant death with dysgenesis of the testes syndrome OMIM:608800
  • sudden infant death-dysgenesis of the testes syndrome MONDO:0012124
Tags
for-review
OMIM
604714
Clinvar variants
Variants in TSPYL1
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

11 Jan 2021, Gel status: 2

Entity classified by Genomics England curator

Eleanor Williams (Genomics England Curator)

Gene: tspyl1 has been classified as Amber List (Moderate Evidence).

11 Jan 2021, Gel status: 2

Set Phenotypes

Eleanor Williams (Genomics England Curator)

Phenotypes for gene: TSPYL1 were changed from Sudden infant death with dysgenesis of the testes syndrome 608800 to Sudden infant death with dysgenesis of the testes syndrome OMIM:608800; sudden infant death-dysgenesis of the testes syndrome MONDO:0012124

11 Jan 2021, Gel status: 2

Set publications

Eleanor Williams (Genomics England Curator)

Publications for gene: TSPYL1 were set to 15273283; 22137496; 19463995

11 Jan 2021, Gel status: 2

Added Tag

Eleanor Williams (Genomics England Curator)

Tag for-review tag was added to gene: TSPYL1.

8 May 2019, Gel status: 2

Entity classified by Genomics England curator

Ivone Leong (Genomics England Curator)

Gene: tspyl1 has been classified as Amber List (Moderate Evidence).

21 Dec 2016, Gel status: 1

panel promoted to version 1

Sarah Leigh (Genomics England Curator)

Promoted to V1 21/12/2016

3 Nov 2016, Gel status: 1

Gene classified by Genomics England curator

Sarah Leigh (Genomics England Curator)

This gene has been classified as Red List (Low Evidence).

3 Nov 2016, Gel status: 1

Gene classified by Genomics England curator

Sarah Leigh (Genomics England Curator)

This gene has been classified as Red List (Low Evidence).

3 Nov 2016, Gel status: 1

Gene classified by Genomics England curator

Sarah Leigh (Genomics England Curator)

This gene has been classified as Red List (Low Evidence).

2 Nov 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).

2 Nov 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).

2 Nov 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).

2 Nov 2016, Gel status: 1

Set publications

Sarah Leigh (Genomics England Curator)

Publications for TSPYL1 were set to 15273283; 22137496; 19463995

23 May 2016, Gel status: 1

Approved Gene

Sarah Leigh (Genomics England Curator)

This proposed gene was validated and added to this panel

23 May 2016, Gel status: 0

Set Phenotypes

Sarah Leigh (Genomics England Curator)

Phenotypes for gene TSPYL1 were set to Sudden infant death with dysgenesis of the testes syndrome 608800

23 May 2016, Gel status: 0

Upload gene information

Sarah Leigh (Genomics England Curator)

TSPYL1 was added to Disorders of sex developmentpanel. Sources: Expert list,Other,Radboud University Medical Center, Nijmegen

23 May 2016, Gel status: 0

clearsources

Sarah Leigh (Genomics England Curator)

TSPYL1All sources for gene: TSPYL1 were removed

23 May 2016, Gel status: 0

Upload gene information

Sarah Leigh (Genomics England Curator)

TSPYL1 was added to Disorders of sex developmentpanel. Sources: Other,Radboud University Medical Center, Nijmegen

23 May 2016, Gel status: 0

Upload gene information

Sarah Leigh (Genomics England Curator)

TSPYL1 was added to Disorders of sex developmentpanel. Sources: Illumina TruGenome Clinical Sequencing Services,Other,UKGTN

23 May 2016, Gel status: 0

Upload gene information

Sarah Leigh (Genomics England Curator)

TSPYL1 was added to Disorders of sex developmentpanel. Sources: Other,Radboud University Medical Center, Nijmegen

4 Feb 2016, Gel status: 0

Added New Source

John Achermann (UCL Institute of Child Health)

TSPYL1 was added to Disorders of sex developmentpanel. Sources: Expert Review

4 Feb 2016, Gel status: 0

Created

John Achermann (UCL Institute of Child Health)

TSPYL1 was created by John Achermann