ClinVar Genomic variation as it relates to human health
NM_000441.2(SLC26A4):c.296C>G (p.Thr99Arg)
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.296C>G (p.Thr99Arg)
Variation ID: 417623 Accession: VCV000417623.6
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 7q22.3 7: 107663427 (GRCh38) [ NCBI UCSC ] 7: 107303872 (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 Apr 17, 2017 Mar 1, 2020 Aug 20, 2019 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000441.2:c.296C>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000432.1:p.Thr99Arg missense NC_000007.14:g.107663427C>G NC_000007.13:g.107303872C>G NG_008489.1:g.7793C>G - Protein change
- T99R
- Other names
- -
- Canonical SPDI
- NC_000007.14:107663426:C:G
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- variation affecting protein structure Variation Ontology [VariO:0060]
- loss_of_function_variant Sequence Ontology [SO:0002054]
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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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0.00060 (T)
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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
Help
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
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. |
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SLC26A4 | - | - |
GRCh38 GRCh37 |
1340 | 1535 |
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. |
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Pathogenic; Affects (2) |
no assertion criteria provided
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Aug 20, 2019 | RCV000460029.4 |
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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Pathogenic
(Jan 03, 2017)
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no assertion criteria provided
Method: clinical testing, research
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Autosomal recessive nonsyndromic hearing loss 4
(Autosomal recessive inheritance)
Affected status: yes, not applicable
Allele origin:
inherited,
not applicable
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Hearing and Balance Clinic, First Affliiated Hospital of Kunming Medical University
Accession: SCV000538187.1
First in ClinVar: Apr 17, 2017 Last updated: Apr 17, 2017 |
Comment:
The proband and his eldest sister were profound hearing loss, and his father, mother and elder sister were normal hearing.
Observation 1:
Clinical Features:
ENLARGED VESTIBULAR AQUEDUCT (present)
Age: 0-9 years
Sex: male
Ethnicity/Population group: Han
Geographic origin: Yunnan Province
Method: DNA samples were extracted from the blood samples using QIAGEN DNA Blood Mini Kit (Cat#51106, QIAGEN Co., Ltd.) following the Handbook. OD260, OD280 value was determined using NanoDrop® instrument and the OD260/OD280 ratio should be around 1.8~2.0 to be good enough for the following sequencing process. Sequencing was done using the Trusight One sequencing panel on the illumina NextSeq 500 platform to analysis inherited hearing loss related genes. The sequencing reads were mapped to the hg19 reference using bwa, variant calling was done using samtools (0.1.19), picard (1.123), and GATK (3.3-0-g37228af). After Trusight One sequencing, the result was verified by the Sanger DNA sequencing technology. The sequencing data were analyzed using the ANNOVAR software. Several databases were used for annotation, including dbSNP, HGMD, ClinVar, 1000G and ESP6500.Annotation of the variants followed the ACMG guidelines
Observation 2:
Comment on evidence:
Our study indicates that a novel c.296C>G variation is the disease-causing mutation in this family as a compound heterozygous mutation with c.919-2A>G.
Method: DNA samples were extracted from the blood samples using QIAGEN DNA Blood Mini Kit (Cat#51106, QIAGEN Co., Ltd.) following the Handbook. OD260, OD280 value was determined using NanoDrop® instrument and the OD260/OD280 ratio should be around 1.8~2.0 to be good enough for the following sequencing process. Sequencing was done using the Trusight One sequencing panel on the illumina NextSeq 500 platform to analysis inherited hearing loss related genes. The sequencing reads were mapped to the hg19 reference using bwa, variant calling was done using samtools (0.1.19), picard (1.123), and GATK (3.3-0-g37228af). After Trusight One sequencing, the result was verified by the Sanger DNA sequencing technology. The sequencing data were analyzed using the ANNOVAR software. Several databases were used for annotation, including dbSNP, HGMD, ClinVar, 1000G and ESP6500.Annotation of the variants followed the ACMG guidelines
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Affects
(Aug 20, 2019)
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no assertion criteria provided
Method: literature only, in vitro
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Autosomal recessive nonsyndromic hearing loss 4
(Autosomal recessive inheritance)
Affected status: yes, unknown
Allele origin:
germline
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National Institute of Sensory Organs, National Hospital Organization Tokyo Medical Center
Additional submitter:
The Hugh Knowles Center for Clinical and Basic Science in Hearing and Its Disorders, Northwestern University
Accession: SCV000994862.2
First in ClinVar: Mar 01, 2020 Last updated: Mar 01, 2020 |
Comment:
in vitro experiment
Observation 1: Observation 2:
Result:
HCO3-/Cl- exchange_impaired; I-/Cl- exchange_impaired; signal at cell membrane_negative; intracellular puncta_negative
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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. |
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variation affecting protein structure
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Hearing and Balance Clinic, First Affliiated Hospital of Kunming Medical University
Accession: SCV000538187.1
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loss_of_function_variant
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National Institute of Sensory Organs, National Hospital Organization Tokyo Medical Center
Additional submitter:
The Hugh Knowles Center for Clinical and Basic Science in Hearing and Its Disorders, Northwestern University
Accession: SCV000994862.2
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Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Systematic quantification of the anion transport function of pendrin (SLC26A4) and its disease-associated variants. | Wasano K | Human mutation | 2020 | PMID: 31599023 |
Mapping pathogenic mutations suggests an innovative structural model for the pendrin (SLC26A4) transmembrane domain. | Bassot C | Biochimie | 2017 | PMID: 27771369 |
SLC26A4 gene is frequently involved in nonsyndromic hearing impairment with enlarged vestibular aqueduct in Caucasian populations. | Albert S | European journal of human genetics : EJHG | 2006 | PMID: 16570074 |
Text-mined citations for rs141142414 ...
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.