VCV002572174.1 - ClinVar

NM_003064.4(SLPI):c.394+1G>T

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

criteria provided, single submitter

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_003064.4(SLPI):c.394+1G>T

Variation ID: 2572174 Accession: VCV002572174.1

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 20q13.12 20: 45253001 (GRCh38) [ NCBI UCSC ] 20: 43881642 (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 26, 2024	Jan 26, 2024	Jul 14, 2023

HGVS

Nucleotide	Protein	Molecular consequence
NM_003064.4:c.394+1G>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.		splice donor
NC_000020.11:g.45253001C>A
NC_000020.10:g.43881642C>A
NG_028137.1:g.6565G>T

Protein change

Other names

Canonical SPDI

NC_000020.11:45253000:C:A

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

effect on RNA splicing; Variation Ontology [ VariO:0362]

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

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.
SLPI		-	-	GRCh38 GRCh37	8	18

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.
Otitis media, susceptibility to	Pathogenic (1)	criteria provided, single submitter	Jul 14, 2023	RCV003482915.1

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 (Jul 14, 2023)	criteria provided, single submitter (Frank et al. (J Med Genet. 2021)) Method: research	Otitis media, susceptibility to (Autosomal dominant inheritance) Affected status: not applicable, yes Allele origin: germline, not applicable	Santos-Cortez Lab, University of Colorado School of Medicine Accession: SCV004012948.1 First in ClinVar: Jan 26, 2024 Last updated: Jan 26, 2024	Comment: The pathogenicity of SLPI NM_003064:c.394+1G>T is strongly supported by a significant LOD score supporting co-segregation with the otitis media phenotype, alternative splicing based on functional … (more) The pathogenicity of SLPI NM_003064:c.394+1G>T is strongly supported by a significant LOD score supporting co-segregation with the otitis media phenotype, alternative splicing based on functional assay on saliva from wildtype vs heterozygous vs homozygous, differentially expressed infection or immune genes according to changes in RNA levels of SLPI in an independent otitis media cohort, microbiota studies of the middle ear and nasopharynx, and cell-specific expression in mouse middle ear after acute infection. (less) Observation 1: Number of individuals with the variant: 55 Clinical Features: Otitis media (present) Age: 1-90 years Sex: mixed Ethnicity/Population group: Indigenous Geographic origin: Philippines Observation 2: Sex: mixed Tissue: Saliva RNA Result: Exon skipping in homozygote due to splice variant.

Comment:

The pathogenicity of SLPI NM_003064:c.394+1G>T is strongly supported by a significant LOD score supporting co-segregation with the otitis media phenotype, alternative splicing based on functional assay on saliva from wildtype vs heterozygous vs homozygous, differentially expressed infection or immune genes according to changes in RNA levels of SLPI in an independent otitis media cohort, microbiota studies of the middle ear and nasopharynx, and cell-specific expression in mouse middle ear after acute infection.

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.
effect on RNA splicing (VariO:0362)	Method not provided Method not provided	Result not provided Exon skipping in homozygote due to splice variant.	Santos-Cortez Lab, University of Colorado School of Medicine Accession: SCV004012948.1

Comment:

Citations for germline classification of this variant

There are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar.

Text-mined citations for this variant ...

Record last updated Feb 14, 2024

ClinVar Genomic variation as it relates to human health

NM_003064.4(SLPI):c.394+1G>T

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...