ClinVar Genomic variation as it relates to human health
NM_000441.2(SLC26A4):c.164+1del
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.
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.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000441.2(SLC26A4):c.164+1del
Variation ID: 188838 Accession: VCV000188838.19
- Type and length
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Deletion, 1 bp
- Location
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Cytogenetic: 7q22.3 7: 107661805 (GRCh38) [ NCBI UCSC ] 7: 107302250 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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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 Mar 29, 2015 Feb 14, 2024 Feb 22, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000441.2:c.164+1del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
splice donor NM_000441.1:c.164+1delG NC_000007.14:g.107661806del NC_000007.13:g.107302251del NG_008489.1:g.6172del - Protein change
- Other names
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- Canonical SPDI
- NC_000007.14:107661804:GG:G
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe 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.
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Allele frequency
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The frequency of the allele represented by this VCV record.
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Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
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Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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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
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The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
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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. |
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SLC26A4 | - | - |
GRCh38 GRCh37 |
1340 | 1535 |
Conditions - Germline
Condition
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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
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Likely pathogenic (3) |
criteria provided, multiple submitters, no conflicts
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Sep 5, 2021 | RCV000169187.8 | |
Pathogenic (1) |
criteria provided, single submitter
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May 14, 2021 | RCV001040907.9 | |
Pathogenic (3) |
criteria provided, multiple submitters, no conflicts
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Feb 22, 2023 | RCV003330085.3 |
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. |
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Likely pathogenic
(Sep 05, 2021)
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criteria provided, single submitter
Method: clinical testing
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Pendred syndrome
Affected status: no
Allele origin:
germline
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Genome-Nilou Lab
Accession: SCV002026520.1
First in ClinVar: Nov 29, 2021 Last updated: Nov 29, 2021 |
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Likely pathogenic
(Jun 19, 2014)
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criteria provided, single submitter
Method: literature only
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Pendred's syndrome
(Autosomal recessive inheritance)
Affected status: unknown
Allele origin:
unknown
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Counsyl
Accession: SCV000220430.2
First in ClinVar: Mar 29, 2015 Last updated: Dec 24, 2022 |
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Pathogenic
(-)
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criteria provided, single submitter
Method: not provided
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Autosomal recessive nonsyndromic hearing loss 4
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
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Institute for Medical Genetics and Human Genetics, Charité - Universitätsmedizin Berlin
Accession: SCV004037138.1
First in ClinVar: Sep 30, 2023 Last updated: Sep 30, 2023 |
Clinical Features:
Sensorineural hearing loss disorder (present) , Global developmental delay (present) , Infantile onset (present) , Autosomal recessive inheritance (present)
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Pathogenic
(Feb 22, 2023)
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criteria provided, single submitter
Method: clinical testing
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Autosomal recessive nonsyndromic hearing loss 4
Affected status: unknown
Allele origin:
unknown
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Baylor Genetics
Accession: SCV004204212.1
First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023 |
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Pathogenic
(May 14, 2021)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV001204498.5
First in ClinVar: Apr 15, 2020 Last updated: Feb 14, 2024 |
Comment:
This variant has been observed in individual(s) with clinical features of Pendred syndrome (PMID: 22717225, 27861301). In at least one individual the data is consistent … (more)
This variant has been observed in individual(s) with clinical features of Pendred syndrome (PMID: 22717225, 27861301). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. This variant is also known as IVS2+1delG. ClinVar contains an entry for this variant (Variation ID: 188838). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. This sequence change creates a premature translational stop signal (p.Ser55Ilefs*11) in the SLC26A4 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SLC26A4 are known to be pathogenic (PMID: 16283880, 25394566, 26252218, 26445815). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Oct 09, 2023)
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no assertion criteria provided
Method: clinical testing
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Autosomal recessive nonsyndromic hearing loss 4
Affected status: yes
Allele origin:
germline
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Zotz-Klimas Genetics Lab, MVZ Zotz Klimas
Accession: SCV004041807.1
First in ClinVar: Oct 14, 2023 Last updated: Oct 14, 2023 |
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Pathogenic
(Jul 29, 2021)
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no assertion criteria provided
Method: clinical testing
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Pendred syndrome
Affected status: unknown
Allele origin:
germline
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Natera, Inc.
Accession: SCV002079962.1
First in ClinVar: Apr 23, 2022 Last updated: Apr 23, 2022 |
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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
HelpTitle | Author | Journal | Year | Link |
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A Novel Mutation in SLC26A4 Causes Nonsyndromic Autosomal Recessive Hearing Impairment. | Wolf A | Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology | 2017 | PMID: 27861301 |
Characterising the spectrum of autosomal recessive hereditary hearing loss in Iran. | Sloan-Heggen CM | Journal of medical genetics | 2015 | PMID: 26445815 |
Mutation Spectrum of Common Deafness-Causing Genes in Patients with Non-Syndromic Deafness in the Xiamen Area, China. | Jiang Y | PloS one | 2015 | PMID: 26252218 |
Evaluation of genotype-phenotype relationships in patients referred for endocrine assessment in suspected Pendred syndrome. | Soh LM | European journal of endocrinology | 2015 | PMID: 25394566 |
Molecular etiology of hearing impairment associated with nonsyndromic enlarged vestibular aqueduct in East China. | Chai Y | American journal of medical genetics. Part A | 2013 | PMID: 23918157 |
Novel mutations in the SLC26A4 gene. | Busi M | International journal of pediatric otorhinolaryngology | 2012 | PMID: 22717225 |
Assessment of the genetic causes of recessive childhood non-syndromic deafness in the UK - implications for genetic testing. | Hutchin T | Clinical genetics | 2005 | PMID: 16283880 |
Text-mined citations for rs786204504 ...
HelpRecord last updated Apr 06, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.