VCV000805870.7 - ClinVar

NM_003309.4(TSPYL1):c.725_726del (p.Val242fs)

Germline

Classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

(5)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Pathogenic/Likely pathogenic

criteria provided, multiple submitters, no conflicts

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_003309.4(TSPYL1):c.725_726del (p.Val242fs)

Variation ID: 805870 Accession: VCV000805870.7

Type and length

Microsatellite, 2 bp

Location

Cytogenetic: 6q22.1 6: 116279105-116279106 (GRCh38) [ NCBI UCSC ] 6: 116600268-116600269 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Jan 24, 2020	Oct 13, 2024	Sep 22, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_003309.4:c.725_726del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_003300.1:p.Val242fs	frameshift
NM_001322937.2:c.-54+20140_-54+20141del		intron variant
NM_001322938.2:c.-54+20140_-54+20141del		intron variant
NM_001322940.2:c.-611+20140_-611+20141del		intron variant
NM_001374520.1:c.-954+20140_-954+20141del		intron variant
NM_001374521.1:c.-641+20140_-641+20141del		intron variant
NM_001374522.1:c.-54+20140_-54+20141del		intron variant
NM_003309.3:c.725_726del		frameshift
NM_003309.3:c.725_726delTG		frameshift
NC_000006.12:g.116279105CA[1]
NC_000006.11:g.116600268CA[1]
NG_016217.1:g.6010TG[1]
NG_033266.4:g.29935CA[1]
LRG_1184:g.29935CA[1]
LRG_862:g.6010TG[1]
LRG_862t1:c.723_724TG[1]	LRG_862p1:p.Val242Glufs

... more HGVS ... less HGVS

Protein change

V242fs

Other names

Canonical SPDI

NC_000006.12:116279104:CACA:CA

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

RNA degradation by nonsense-mediated decay; Variation Ontology [ VariO:0347]

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

Allele frequency Help The frequency of the allele represented by this VCV record.

Links

OMIM: 604714.0002 dbSNP: rs775957625 VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
DSE		-	-	GRCh38 GRCh37	344	429
TSPYL1		-	-	GRCh38 GRCh37	-	82

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
Sudden infant death-dysgenesis of the testes syndrome	Pathogenic/Likely pathogenic (5)	criteria provided, multiple submitters, no conflicts	Sep 22, 2024	RCV000993688.16

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Likely pathogenic (May 14, 2020)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Sudden infant death-dysgenesis of the testes syndrome Affected status: yes Allele origin: inherited	Equipe Genetique des Anomalies du Developpement, Université de Bourgogne Accession: SCV001450719.1 First in ClinVar: Dec 17, 2020 Last updated: Dec 17, 2020 Comment: compound heterozygous c.[725_726del;236del]	Clinical Features: Sudden infant death (present) , Sex development disorder (present) , Morphological features (present) , Epilepsy (present)
Pathogenic (May 17, 2019)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Sudden infant death-dysgenesis of the testes syndrome Affected status: yes Allele origin: maternal	Baylor Genetics Accession: SCV001521184.1 First in ClinVar: Mar 22, 2021 Last updated: Mar 22, 2021	Comment: This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868].
Pathogenic (Sep 22, 2024)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Sudden infant death-dysgenesis of the testes syndrome Affected status: unknown Allele origin: germline	Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center Accession: SCV005374137.1 First in ClinVar: Oct 13, 2024 Last updated: Oct 13, 2024
Pathogenic (Jan 10, 2020)	no assertion criteria provided Method: clinical testing	Sudden infant death-dysgenesis of the testes syndrome (Autosomal recessive inheritance) Affected status: yes Allele origin: inherited	Department of Molecular and Human Genetics, Baylor College of Medicine Accession: SCV001142567.1 First in ClinVar: Jan 24, 2020 Last updated: Jan 24, 2020
Pathogenic (Oct 21, 2021)	no assertion criteria provided Method: literature only	SUDDEN INFANT DEATH WITH DYSGENESIS OF THE TESTES SYNDROME Affected status: not provided Allele origin: germline	OMIM Accession: SCV001981690.1 First in ClinVar: Oct 25, 2021 Last updated: Oct 25, 2021	Publications: PubMed (1) PubMed: 32885560 Comment on evidence: In a non-Amish 46,XY phenotypically female infant with sudden infant death and testicular dysgenesis syndrome (SIDDT; 608800), Slater et al. (2020) identified homozygosity for a … (more) In a non-Amish 46,XY phenotypically female infant with sudden infant death and testicular dysgenesis syndrome (SIDDT; 608800), Slater et al. (2020) identified homozygosity for a 2-bp deletion (c.725_726delTG, NM_003309.3) in the TSPYL1 gene, causing a frameshift predicted to result in a premature termination codon (Val242GlufsTer52). Her unaffected mother was heterozygous for the mutation; DNA was unavailable from the father for analysis. The 2-bp deletion was present at low minor allele frequency (0.002%) in the gnomAD database, in only heterozygous state. (less)

Germline Functional Evidence

Functional Help The functional consequence of the variant, based on experimental evidence and provided by the submitter. consequence	Method Help A brief description of the method used to determine the functional consequence of the variant. A citation for the method is included, when provided by the submitter.	Result Help A brief description of the result of this method for this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting functional evidence for the germline classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
RNA degradation by nonsense-mediated decay (VariO:0347)			Department of Molecular and Human Genetics, Baylor College of Medicine Accession: SCV001142567.1

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Sudden infant death with dysgenesis of the testes syndrome in a non-Amish infant: A case report.	Slater B	American journal of medical genetics. Part A	2020	PMID: 32885560

Text-mined citations for rs775957625 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Nov 25, 2024

ClinVar Genomic variation as it relates to human health

NM_003309.4(TSPYL1):c.725_726del (p.Val242fs)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs775957625 ...