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rs148882860

Variant summary

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

The NM_139319.3(SLC17A8):c.858T>C(p.Tyr286=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000415 in 1,614,112 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0023 ( 3 hom., cov: 32)
Exomes 𝑓: 0.00021 ( 3 hom. )

Consequence

SLC17A8
NM_139319.3 synonymous

Scores

2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.117
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]

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=-0.82).
BP6
Variant 12-100402434-T-C is Benign according to our data. Variant chr12-100402434-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 198617.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=0.117 with no splicing effect.
BS2
High AC in GnomAd at 355 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SLC17A8NM_139319.3 linkuse as main transcriptc.858T>C p.Tyr286= synonymous_variant 7/12 ENST00000323346.10
SLC17A8NM_001145288.2 linkuse as main transcriptc.858T>C p.Tyr286= synonymous_variant 7/11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SLC17A8ENST00000323346.10 linkuse as main transcriptc.858T>C p.Tyr286= synonymous_variant 7/121 NM_139319.3 P1Q8NDX2-1
SLC17A8ENST00000392989.3 linkuse as main transcriptc.858T>C p.Tyr286= synonymous_variant 7/111 Q8NDX2-2

Frequencies

GnomAD3 genomes
AF:
0.00233
AC:
355
AN:
152140
Hom.:
3
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00799
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00138
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00143
GnomAD3 exomes
AF:
0.000606
AC:
152
AN:
250764
Hom.:
1
AF XY:
0.000524
AC XY:
71
AN XY:
135500
show subpopulations
Gnomad AFR exome
AF:
0.00825
Gnomad AMR exome
AF:
0.000405
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000653
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000884
Gnomad OTH exome
AF:
0.000164
GnomAD4 exome
AF:
0.000215
AC:
314
AN:
1461854
Hom.:
3
Cov.:
32
AF XY:
0.000212
AC XY:
154
AN XY:
727230
show subpopulations
Gnomad4 AFR exome
AF:
0.00762
Gnomad4 AMR exome
AF:
0.000626
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000464
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000270
Gnomad4 OTH exome
AF:
0.000397
GnomAD4 genome
AF:
0.00234
AC:
356
AN:
152258
Hom.:
3
Cov.:
32
AF XY:
0.00248
AC XY:
185
AN XY:
74466
show subpopulations
Gnomad4 AFR
AF:
0.00799
Gnomad4 AMR
AF:
0.00137
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00142
Alfa
AF:
0.00140
Hom.:
0
Bravo
AF:
0.00258
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:3
Benign, criteria provided, single submitterclinical testingInvitaeNov 28, 2023- -
Benign, criteria provided, single submitterclinical testingGeneDxMar 31, 2020- -
Benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenFeb 01, 2023SLC17A8: BP4, BP7, BS1, BS2 -
not specified Benign:2
Benign, criteria provided, single submitterclinical testingEurofins Ntd Llc (ga)Jan 29, 2015- -
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact Sciences-- -
Autosomal dominant nonsyndromic hearing loss 25 Benign:2
Likely benign, criteria provided, single submitterclinical testingFulgent Genetics, Fulgent GeneticsSep 08, 2021- -
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 12, 2018This 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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.82
Cadd
Benign
0.91
Dann
Benign
0.64

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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.

Other links and lift over

dbSNP: rs148882860; hg19: chr12-100796212; API