rs11568546

Positions:

chr12-100380935-T-C

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The ENST00000323346.10(SLC17A8):c.336T>C(p.Asp112=) 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
ENST00000323346.10 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.596

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 [Likely_benign]. Clinvar id is 47883.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-100380935-T-C is described in Lovd as [Likely_benign]. Variant chr12-100380935-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.596 with no splicing effect.

BS2

High AC in GnomAd4 at 397 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC17A8	NM_139319.3 linkuse as main transcript	c.336T>C	p.Asp112=	synonymous_variant	2/12	ENST00000323346.10	NP_647480.1
SLC17A8	NM_001145288.2 linkuse as main transcript	c.336T>C	p.Asp112=	synonymous_variant	2/11		NP_001138760.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC17A8	ENST00000323346.10 linkuse as main transcript	c.336T>C	p.Asp112=	synonymous_variant	2/12	1	NM_139319.3	ENSP00000316909	P1	Q8NDX2-1
SLC17A8	ENST00000392989.3 linkuse as main transcript	c.336T>C	p.Asp112=	synonymous_variant	2/11	1		ENSP00000376715		Q8NDX2-2

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

GnomAD3 exomes

AF:

0.00275

AC:

692

AN:

251426

Hom.:

AF XY:

0.00275

AC XY:

374

AN XY:

135886

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 SAS exome

AF:

0.00150

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

Gnomad4 AFR exome

AF:

0.000687

Gnomad4 AMR exome

AF:

0.00170

Gnomad4 ASJ exome

AF:

0.00122

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00161

Gnomad4 FIN exome

AF:

0.00150

Gnomad4 NFE exome

AF:

0.00360

Gnomad4 OTH exome

AF:

0.00325

GnomAD4 genome

AF:

0.00261

AC:

397

AN:

152270

Hom.:

Cov.:

AF XY:

0.00228

AC XY:

170

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.000794

Gnomad4 AMR

AF:

0.00190

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.000848

Gnomad4 NFE

AF:

0.00401

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00340

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

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	May 01, 2024	SLC17A8: BP4, BP7 -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 07, 2024	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 14, 2021	- -

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Dec 03, 2019	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	May 07, 2012	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

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

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

DANN

Benign

0.61

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over