6-116279104-TCA-T
Variant summary
Our verdict is Pathogenic. Variant got 14 ACMG points: 14P and 0B. PVS1_StrongPM2PP5_Very_Strong
The NM_003309.4(TSPYL1):c.725_726del(p.Val242GlufsTer52) variant causes a frameshift change. The variant allele was found at a frequency of 0.0000328 in 1,614,076 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (★★).
Frequency
Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000034 ( 0 hom. )
Consequence
TSPYL1
NM_003309.4 frameshift
NM_003309.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 5.38
Genes affected
TSPYL1 (HGNC:12382): (TSPY like 1) The protein encoded by this gene is found in the nucleolus and is similar to that of a family of genes on the Y-chromosome. This gene is intronless. Defects in this gene are a cause of sudden infant death with dysgenesis of the testes syndrome (SIDDT). [provided by RefSeq, Dec 2009]
DSE (HGNC:21144): (dermatan sulfate epimerase) The protein encoded by this gene is a tumor-rejection antigen. It is localized to the endoplasmic reticulum and functions to convert D-glucuronic acid to L-iduronic acid during the biosynthesis of dermatan sulfate. This antigen possesses tumor epitopes capable of inducing HLA-A24-restricted and tumor-specific cytotoxic T lymphocytes in cancer patients and may be useful for specific immunotherapy. Mutations in this gene cause inmusculocontractural Ehlers-Danlos syndrome. Alternative splicing results in multiple transcript variants. A related pseudogene has been identified on chromosome 9, and a paralogous gene exists on chromosome 18. [provided by RefSeq, Apr 2016]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 14 ACMG points.
PVS1
?
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.448 CDS is truncated, and there are 0 pathogenic variants in the truncated region.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 6-116279104-TCA-T is Pathogenic according to our data. Variant chr6-116279104-TCA-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 805870.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TSPYL1 | NM_003309.4 | c.725_726del | p.Val242GlufsTer52 | frameshift_variant | 1/1 | ENST00000368608.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TSPYL1 | ENST00000368608.4 | c.725_726del | p.Val242GlufsTer52 | frameshift_variant | 1/1 | NM_003309.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152178Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251404Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135868
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GnomAD4 exome AF: 0.0000335 AC: 49AN: 1461780Hom.: 0 AF XY: 0.0000316 AC XY: 23AN XY: 727168
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GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152296Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74462
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ClinVar
Significance: Pathogenic/Likely pathogenic
Submissions summary: Pathogenic:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Sudden infant death-dysgenesis of the testes syndrome Pathogenic:4
Pathogenic, no assertion criteria provided | literature only | OMIM | Oct 21, 2021 | - - |
Pathogenic, no assertion criteria provided | clinical testing | Department of Molecular and Human Genetics, Baylor College of Medicine | Jan 10, 2020 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | May 17, 2019 | This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868]. - |
Likely pathogenic, criteria provided, single submitter | clinical testing | Equipe Genetique des Anomalies du Developpement, Université de Bourgogne | May 14, 2020 | - - |
Computational scores
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at