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Hearing loss

Gene: SLC17A8

Green List (high evidence)

SLC17A8 (solute carrier family 17 member 8)
EnsemblGeneIds (GRCh38): ENSG00000179520
EnsemblGeneIds (GRCh37): ENSG00000179520
OMIM: 607557, Gene2Phenotype
SLC17A8 is in 1 panel

6 reviews

Eleanor Williams (Genomics England Curator)

Comment on list classification: Upgrading from red to green based on new evidence added.
Created: 12 Jun 2019, 11:23 a.m.
Associated with Deafness, autosomal dominant 25 (#605583) in OMIM.

PMID: 18674745 - Ruel et al 2008 - 2 families with autosomal dominant nonsyndromic deafness and a missense mutation (p.A211V)

PMID: 24082139 - Gonzalez-Garay et al 2013 - 81 nonrelated volunteers underwent exome sequencing. Every nonsynonymous coding variant was interrogated for human inherited disease mutations using the HGMD.
A volunteer (patient 3934 - see Table S1) with nonsyndromic deafness was found to have risk alleles in two genes associated with autosomal dominant deafness (MYH14 p.M161I, SLC17A8 p.R75C) and had a three-generation positive family history of deafness.

PMID: 23967202 - Miyagawa et al 2013 - missense mutation (p.A374S) in SLC17A8 in 4 confirmed alleles in 432 patient alleles. Patients had hearing loss. Autosomal dominant.

PMID: 26969326 - Sloan-Heggen et al 2016 - 1 patient with hearing loss with a heterozygous missense variant p.P54L.

PMID: 27610647 - Chen et al 2016 - no access to publication. The gene is not mentioned in the abstract.

PMID: 28314816 - Ramet et al 2017 - mouse model. The A211 alanine in human VGLUTs corresponds to position 224 in the mouse VGLUT3 sequence (A224). The VGLUT3 A224V/A224V mice present the same progressive loss of hearing reported in humans. NOTE: the mouse is homozygous for the variant.

PMID: 30245029 - Azaiez et al 2018 - Deafness Variation Database - list NM_139319:p.Ala374Ser in SLC17A8 as benign.

Summary: >3 cases, all missense variants, mouse model supports the role of this gene in the hearing loss phenotype.
Created: 5 Jun 2019, 10:30 a.m.

Emma Ashton (Great Ormond Street Hospital)

Green List (high evidence)

8 DM mutations HGMD multiple publications. DFNA25 #605583
Ruel et al 2008 PMID 18674745
Gonzalez-Garay et al 2013 PMID 24082139
Miyagawa et al 2013 PMID 23967202
Sloan-Heggen et al 2016 PMID 26969326
Chen et al 2016 PMID 27610647
Ramet et al 2017 PMID 28314816
Azaiez et al 2018 PMID 30245029
Created: 17 Feb 2019, 4:35 p.m.

Maria Bitner-Glindzicz (UCL)

Green List (high evidence)

Ellen McDonagh (Genomics England Curator)

Comment on list classification: Confirmed with the first reviewer that this should remain as red as less convincing evidence than established green genes.
Created: 2 Mar 2016, 11:22 a.m.

Jun Shen (Harvard Medical School)

Red List (low evidence)

Only 3 missense variants reported in humans (according to HGMD), including one at a frequency of ~0.5% (1 in 200) which is too high for a congenital dominant gene to cause profound/severe hearing loss. The function of the other two missense variants have not been assessed. The knockout mouse model suggests an autosomal recessive loss-of-function mechanism, but the human data suggest autosomal dominant inheritance. Affected individuals with DFNA25 associated hearing loss typically manifest a high-frequency, slowly progressive sensorineural hearing loss in the postlingual period (PMID 12925340).
Created: 24 Feb 2016, 10:42 p.m.

Mode of inheritance
Unknown

Phenotypes
#605583:Deafness, autosomal dominant 25

Publications

Damian Smedley (Genomics England Curator)

Comment when marking as ready: Expert review and OMIM confirmed
Created: 29 Jan 2016, 4:19 p.m.

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Expert Review Green
  • Expert
  • Radboud University Medical Center, Nijmegen
  • Emory Genetics Laboratory
  • UKGTN
  • Illumina TruGenome Clinical Sequencing Services
Phenotypes
  • hearing loss
  • Nonsyndromic Hearing Loss, Dominant
  • Deafness, autosomal dominant 25, 605583
OMIM
607557
Clinvar variants
Variants in SLC17A8
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

12 Jun 2019, Gel status: 3

Entity classified by Genomics England curator

Eleanor Williams (Genomics England Curator)

Gene: slc17a8 has been classified as Green List (High Evidence).

5 Jun 2019, Gel status: 1

Set publications

Eleanor Williams (Genomics England Curator)

Publications for gene: SLC17A8 were set to PMID: 12151341; 18215623; 18674745; 19915548; 9323205

2 Mar 2016, Gel status: 1

Gene classified by Genomics England curator

Ellen McDonagh (Genomics England Curator)

This gene has been classified as Red List (Low Evidence).

2 Mar 2016, Gel status: 1

Gene classified by Genomics England curator

Ellen McDonagh (Genomics England Curator)

This gene has been classified as Red List (Low Evidence).

1 Mar 2016, Gel status: 2

Gene classified by Genomics England curator

Ellen McDonagh (Genomics England Curator)

This gene has been classified as Amber List (Moderate Evidence).

1 Mar 2016, Gel status: 2

Gene classified by Genomics England curator

Ellen McDonagh (Genomics England Curator)

This gene has been classified as Amber List (Moderate Evidence).

22 Feb 2016, Gel status: 4

Set publications

Ellen McDonagh (Genomics England Curator)

Publications for SLC17A8 were set to PMID: 12151341; 18215623; 18674745; 19915548; 9323205

29 Jan 2016, Gel status: 4

Gene classified by Genomics England curator

Damian Smedley (Genomics England Curator)

This gene has been classified as Green List (High Evidence).

24 Jun 2015, Gel status: 4

Set Mode of Inheritance

Ellen McDonagh (Genomics England Curator)

Model of inheritance for gene SLC17A8 was changed to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

24 Jun 2015, Gel status: 4

Added New Source

Ellen McDonagh (Genomics England Curator)

SLC17A8 was added to Congenital hearing impairment (Profound/Severe)panel. Sources: Illumina TruGenome Clinical Sequencing Services,UKGTN,Emory Genetics Laboratory,Radboud University Medical Center, Nijmegen,Expert

24 Jun 2015, Gel status: 4

Set Mode of Inheritance

Ellen McDonagh (Genomics England Curator)

Model of inheritance for gene SLC17A8 was changed to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

24 Jun 2015, Gel status: 4

Added New Source

Ellen McDonagh (Genomics England Curator)

SLC17A8 was added to Congenital hearing impairment (Profound/Severe)panel. Sources: Illumina TruGenome Clinical Sequencing Services,UKGTN,Emory Genetics Laboratory,Radboud University Medical Center, Nijmegen,Expert

24 Jun 2015, Gel status: 3

Set Mode of Inheritance

Ellen McDonagh (Genomics England Curator)

Model of inheritance for gene SLC17A8 was changed to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

24 Jun 2015, Gel status: 3

Added New Source

Ellen McDonagh (Genomics England Curator)

SLC17A8 was added to Congenital hearing impairment (Profound/Severe)panel. Sources: Illumina TruGenome Clinical Sequencing Services,UKGTN,Emory Genetics Laboratory,Radboud University Medical Center, Nijmegen,Expert

24 Jun 2015, Gel status: 2

Set Mode of Inheritance

Ellen McDonagh (Genomics England Curator)

Model of inheritance for gene SLC17A8 was changed to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

24 Jun 2015, Gel status: 2

Added New Source

Ellen McDonagh (Genomics England Curator)

SLC17A8 was added to Congenital hearing impairment (Profound/Severe)panel. Sources: Illumina TruGenome Clinical Sequencing Services,UKGTN,Emory Genetics Laboratory,Radboud University Medical Center, Nijmegen,Expert

24 Jun 2015, Gel status: 1

Added New Source

Ellen McDonagh (Genomics England Curator)

SLC17A8 was added to Congenital hearing impairment (Profound/Severe)panel. Sources: Illumina TruGenome Clinical Sequencing Services,UKGTN,Emory Genetics Laboratory,Radboud University Medical Center, Nijmegen,Expert