VCV000005385.3 - ClinVar

NM_003309.4(TSPYL1):c.460dup (p.Glu154fs)

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.

(1)

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

no assertion criteria provided

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_003309.4(TSPYL1):c.460dup (p.Glu154fs)

Variation ID: 5385 Accession: VCV000005385.3

Type and length

Duplication, 1 bp

Location

Cytogenetic: 6q22.1 6: 116279370-116279371 (GRCh38) [ NCBI UCSC ] 6: 116600533-116600534 (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	Apr 4, 2013	Oct 15, 2022	Aug 10, 2004

HGVS

Nucleotide	Protein	Molecular consequence
NM_003309.4:c.460dup MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_003300.1:p.Glu154fs	frameshift
NM_001322937.2:c.-54+20405dup		intron variant
NM_001322938.2:c.-54+20405dup		intron variant
NM_001322940.2:c.-611+20405dup		intron variant
NM_001374520.1:c.-954+20405dup		intron variant
NM_001374521.1:c.-641+20405dup		intron variant
NM_001374522.1:c.-54+20405dup		intron variant
NC_000006.12:g.116279372dup
NC_000006.11:g.116600535dup
NG_016217.1:g.5747dup
NG_033266.4:g.30202dup
NG_176480.1:g.179dup
NG_176481.1:g.109dup
LRG_1184:g.30202dup
LRG_862:g.5747dup
LRG_862t1:c.459dup	LRG_862p1:p.Glu154Glyfs

... more HGVS ... less HGVS

Protein change

E154fs

Other names

Canonical SPDI

NC_000006.12:116279370:CC:CCC

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

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

ClinGen: CA2580074796 OMIM: 604714.0001 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	356	447
LOC129997035	-	-	-	GRCh38	-	29
TSPYL1		-	-	GRCh38 GRCh37	-	88

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 (1)	no assertion criteria provided	Aug 10, 2004	RCV000005716.11

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.
Pathogenic (Aug 10, 2004)	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: SCV000025898.3 First in ClinVar: Apr 04, 2013 Last updated: Oct 15, 2022	Publications: PubMed (1) PubMed: 15273283 Comment on evidence: In affected infants with sudden infant death with dysgenesis of the testes syndrome (SIDDT; 608800) from the Belleville Old Order Amish community, Puffenberger et al. … (more) In affected infants with sudden infant death with dysgenesis of the testes syndrome (SIDDT; 608800) from the Belleville Old Order Amish community, Puffenberger et al. (2004) identified homozygosity for a 1-bp insertion (457G) in the TSPYL1 gene. All parents were heterozygous for the mutation. The mutation results in premature termination of the protein at codon 169 and leads to loss of a peptide domain with strong homology to the nucleosome assembly protein family. Expression studies showed loss of nuclear localization of the truncated protein, suggesting loss of a nuclear localization patch in addition to loss of the nucleosome assembly domain. (less)

Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Mapping of sudden infant death with dysgenesis of the testes syndrome (SIDDT) by a SNP genome scan and identification of TSPYL loss of function.	Puffenberger EG	Proceedings of the National Academy of Sciences of the United States of America	2004	PMID: 15273283

Text-mined citations for this variant ...

Record last updated Jan 26, 2025

ClinVar Genomic variation as it relates to human health

NM_003309.4(TSPYL1):c.460dup (p.Glu154fs)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...