ClinVar Genomic variation as it relates to human health
NM_000441.2(SLC26A4):c.1363A>T (p.Ile455Phe)
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
-
NM_000441.2(SLC26A4):c.1363A>T (p.Ile455Phe)
Variation ID: 43507 Accession: VCV000043507.28
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 7q22.3 7: 107694642 (GRCh38) [ NCBI UCSC ] 7: 107335087 (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 May 29, 2016 Feb 14, 2024 Sep 28, 2018 - HGVS
-
Nucleotide Protein Molecular
consequenceNM_000441.2:c.1363A>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000432.1:p.Ile455Phe missense NC_000007.14:g.107694642A>T NC_000007.13:g.107335087A>T NG_008489.1:g.39008A>T O43511:p.Ile455Phe - Protein change
- I455F
- Other names
- NM_000441.1(SLC26A4):c.1363A>T(p.Ile455Phe)
- NM_000441.1(SLC26A4):c.1363A>T
- Canonical SPDI
- NC_000007.14:107694641:A:T
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
-
-
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.
-
0.00759 (T)
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
The Genome Aggregation Database (gnomAD) 0.00003
Trans-Omics for Precision Medicine (TOPMed) 0.00022
The Genome Aggregation Database (gnomAD), exomes 0.00397
Exome Aggregation Consortium (ExAC) 0.00436
1000 Genomes Project 30x 0.00718
1000 Genomes Project 0.00759
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 | ||
---|---|---|---|---|---|---|
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. |
|||
SLC26A4 | - | - |
GRCh38 GRCh37 |
1332 | 1527 |
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. |
---|---|---|---|---|
Benign (3) |
criteria provided, multiple submitters, no conflicts
|
Mar 3, 2016 | RCV000036441.12 | |
Benign (4) |
criteria provided, multiple submitters, no conflicts
|
Jan 31, 2024 | RCV000441541.12 | |
Benign (3) |
reviewed by expert panel
|
Sep 28, 2018 | RCV000710343.7 | |
Uncertain significance (1) |
criteria provided, single submitter
|
Apr 27, 2017 | RCV001162716.4 | |
Benign (1) |
criteria provided, single submitter
|
- | RCV001258258.2 | |
Likely benign (1) |
criteria provided, single submitter
|
May 5, 2022 | RCV002496560.1 |
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. |
|
---|---|---|---|---|---|
Benign
(Sep 28, 2018)
|
reviewed by expert panel
Method: curation
|
Pendred syndrome
(Autosomal recessive inheritance)
Affected status: unknown
Allele origin:
germline
|
ClinGen Hearing Loss Variant Curation Expert Panel
Accession: SCV000840540.4
First in ClinVar: Oct 20, 2018 Last updated: Dec 11, 2022 |
Comment:
The filtering allele frequency of the p.Ile455Phe variant in the SLC26A4 gene is 3% (981/30778) of South Asian chromosomes by the Genome Aggregation Database (http://gnomad.broadinstitute.org; … (more)
The filtering allele frequency of the p.Ile455Phe variant in the SLC26A4 gene is 3% (981/30778) of South Asian chromosomes by the Genome Aggregation Database (http://gnomad.broadinstitute.org; calculated by using inverse allele frequency at https://www.cardiodb.org/allelefrequencyapp/), which is a high frequency that is consistent with benign classification based on thresholds defined by the ClinGen Hearing Loss Expert Panel for autosomal recessive hearing loss variants (BA1). (less)
|
|
Benign
(Mar 30, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000977459.1
First in ClinVar: Aug 26, 2019 Last updated: Aug 26, 2019 |
Comment:
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at … (more)
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. (less)
|
|
Benign
(Jan 24, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: not provided
Allele origin:
germline
|
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics
Accession: SCV000511788.1
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
|
|
Benign
(Jan 16, 2015)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
germline
|
Eurofins Ntd Llc (ga)
Accession: SCV000225516.5
First in ClinVar: Jun 28, 2015 Last updated: May 29, 2016 |
Sex: mixed
|
|
Benign
(Mar 03, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: not provided
Allele origin:
germline
|
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000060096.6
First in ClinVar: May 03, 2013 Last updated: May 29, 2016 |
Comment:
p.Ile455Phe in exon 12 of SLC26A4: This variant is not expected to have clinical significance because it has been identified in 3.2% (520/16506) of South … (more)
p.Ile455Phe in exon 12 of SLC26A4: This variant is not expected to have clinical significance because it has been identified in 3.2% (520/16506) of South Asian chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitut e.org; dbSNP rs375576481). (less)
Number of individuals with the variant: 6
|
|
Uncertain significance
(Apr 27, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
Autosomal recessive nonsyndromic hearing loss 4
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV001324679.1
First in ClinVar: May 31, 2020 Last updated: May 31, 2020 |
Comment:
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, … (more)
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. (less)
|
|
Uncertain significance
(Apr 27, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
Pendred syndrome
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV001324678.1
First in ClinVar: May 31, 2020 Last updated: May 31, 2020 |
Comment:
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, … (more)
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. (less)
|
|
Benign
(-)
|
criteria provided, single submitter
Method: research
|
Microcephaly 5, primary, autosomal recessive
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
|
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard
Accession: SCV001435172.1
First in ClinVar: Oct 03, 2020 Last updated: Oct 03, 2020 |
Comment:
The p.Ile455Phe variant in SLC26A4 has been identified in at least 2 individuals with non-syndromic deafness (PMID: 12676893), and has been identified in >3% of … (more)
The p.Ile455Phe variant in SLC26A4 has been identified in at least 2 individuals with non-syndromic deafness (PMID: 12676893), and has been identified in >3% of South Asian chromosomes and 13 homozygotes by ExAC (http://gnomad.broadinstitute.org/). In summary, this variant meets criteria to be classified as benign for autosomal recessive non-syndromic deafness. (less)
|
|
Likely benign
(May 05, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Pendred syndrome
Autosomal recessive nonsyndromic hearing loss 4
Affected status: unknown
Allele origin:
unknown
|
Fulgent Genetics, Fulgent Genetics
Accession: SCV002805334.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
|
|
Benign
(Jan 31, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Invitae
Accession: SCV001041168.6
First in ClinVar: Dec 17, 2019 Last updated: Feb 14, 2024 |
|
|
Benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
not specified
Affected status: yes
Allele origin:
germline
|
Clinical Genetics, Academic Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001917618.1 First in ClinVar: Sep 24, 2021 Last updated: Sep 24, 2021 |
|
|
Benign
(Apr 16, 2020)
|
no assertion criteria provided
Method: clinical testing
|
Pendred syndrome
Affected status: unknown
Allele origin:
germline
|
Natera, Inc.
Accession: SCV001459871.1
First in ClinVar: Jan 02, 2021 Last updated: Jan 02, 2021 |
|
|
Likely benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001968386.1 First in ClinVar: Oct 07, 2021 Last updated: Oct 07, 2021 |
|
|
click to load more click to collapse |
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 |
---|---|---|---|---|
SLC26A4 mutation spectrum associated with DFNB4 deafness and Pendred's syndrome in Pakistanis. | Anwar S | Journal of human genetics | 2009 | PMID: 19287372 |
Origins and frequencies of SLC26A4 (PDS) mutations in east and south Asians: global implications for the epidemiology of deafness. | Park HJ | Journal of medical genetics | 2003 | PMID: 12676893 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=SLC26A4 | - | - | - | - |
https://erepo.clinicalgenome.org/evrepo/ui/interpretation/2b9fd19d-de91-41b2-a416-dc26fa5062e4 | - | - | - | - |
Text-mined citations for rs375576481 ...
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.