rs11568546

Variant names:

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_139319.3(SLC17A8):c.336T>C(p.Asp112Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0031 in 1,614,114 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0026 ( 1 hom., cov: 31)

Exomes 𝑓: 0.0032 ( 11 hom. )

Consequence

SLC17A8
NM_139319.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.596

Publications

3 publications found

Variant links:

Genes affected

SLC17A8 (HGNC:20151): (solute carrier family 17 member 8) This gene encodes a vesicular glutamate transporter. The encoded protein transports the neurotransmitter glutamate into synaptic vesicles before it is released into the synaptic cleft. Mutations in this gene are the cause of autosomal-dominant nonsyndromic type 25 deafness. Alternate splicing results in multiple transcript variants.[provided by RefSeq, May 2010]

SLC17A8 Gene-Disease associations (from GenCC):

nonsyndromic genetic hearing loss
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
autosomal dominant nonsyndromic hearing loss 25
Inheritance: AD, Unknown Classification: STRONG, LIMITED Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae)
autosomal dominant nonsyndromic hearing loss
Inheritance: AD Classification: SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet

SLC17A8 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.51).

BP6

Variant 12-100380935-T-C is Benign according to our data. Variant chr12-100380935-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 47883.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.596 with no splicing effect.

BS2

High AC in GnomAd4 at 397 AD,Unknown gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC17A8	NM_139319.3 link	c.336T>C	p.Asp112Asp	synonymous_variant	Exon 2 of 12	ENST00000323346.10	NP_647480.1
SLC17A8	NM_001145288.2 link	c.336T>C	p.Asp112Asp	synonymous_variant	Exon 2 of 11		NP_001138760.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC17A8	ENST00000323346.10 link	c.336T>C	p.Asp112Asp	synonymous_variant	Exon 2 of 12	1	NM_139319.3	ENSP00000316909.4
SLC17A8	ENST00000392989.3 link	c.336T>C	p.Asp112Asp	synonymous_variant	Exon 2 of 11	1		ENSP00000376715.3

Frequencies

GnomAD3 genomes

AF:

0.00262

AC:

398

AN:

152152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000797

Gnomad AMI

AF:

0.0396

Gnomad AMR

AF:

0.00190

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.000848

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.00401

Gnomad OTH

AF:

0.00144

GnomAD2 exomes

AF:

0.00275

AC:

692

AN:

251426

AF XY:

0.00275

show subpopulations

Gnomad AFR exome

AF:

0.000677

Gnomad AMR exome

AF:

0.00150

Gnomad ASJ exome

AF:

0.00119

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00134

Gnomad NFE exome

AF:

0.00461

Gnomad OTH exome

AF:

0.00293

GnomAD4 exome

AF:

0.00315

AC:

4605

AN:

1461844

Hom.:

Cov.:

AF XY:

0.00310

AC XY:

2258

AN XY:

727226

show subpopulations

African (AFR)

AF:

0.000687

AC:

AN:

33480

American (AMR)

AF:

0.00170

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00122

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00161

AC:

139

AN:

86252

European-Finnish (FIN)

AF:

0.00150

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.0106

AC:

AN:

5734

European-Non Finnish (NFE)

AF:

0.00360

AC:

3998

AN:

1112002

Other (OTH)

AF:

0.00325

AC:

196

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

266

531

797

1062

1328

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

142

284

426

568

710

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00261

AC:

397

AN:

152270

Hom.:

Cov.:

AF XY:

0.00228

AC XY:

170

AN XY:

74456

show subpopulations

African (AFR)

AF:

0.000794

AC:

AN:

41536

American (AMR)

AF:

0.00190

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00173

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.000622

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.000848

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00401

AC:

273

AN:

68038

Other (OTH)

AF:

0.00142

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00350

Hom.:

Bravo

AF:

0.00266

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00518

EpiControl

AF:

0.00539

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Sep 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

SLC17A8: BP4, BP7

Jun 14, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Jan 23, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

not specified

Benign:3

Dec 03, 2019

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

May 07, 2012

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Asp112Asp in Exon 02 of SLC17A8: This variant is not expected to have clinical significance because it does not alter an amino acid residue, is not located wit hin the splice consensus sequence, and has been identified in 0.4% (28/7020) of European American chromosomes from a broad population by the NHLBI Exome Sequenc ing Project (http://evs.gs.washington.edu/EVS; dbSNP rs11568546).

Autosomal dominant nonsyndromic hearing loss 25

Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

2.4

(source)

DANN

Benign

0.61

PhyloP100

0.60

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over