Genetic Variant SLC17A8:c.763+58A>G (chr12-100401921-A-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_139319.3(SLC17A8):c.763+58A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.331 in 1,366,948 control chromosomes in the GnomAD database, including 80,868 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.29 ( 7343 hom., cov: 31)

Exomes 𝑓: 0.34 ( 73525 hom. )

Consequence

SLC17A8
NM_139319.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.608

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:

LOC124903108 (HGNC:):

LOC124903108 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 12-100401921-A-G is Benign according to our data. Variant chr12-100401921-A-G is described in ClinVar as [Benign]. Clinvar id is 1247732.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.363 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
SLC17A8	NM_139319.3 link	c.763+58A>G	intron_variant	Intron 6 of 11	ENST00000323346.10	NP_647480.1	Q8NDX2-1
SLC17A8	NM_001145288.2 link	c.763+58A>G	intron_variant	Intron 6 of 10		NP_001138760.1	Q8NDX2-2
LOC124903108	XR_007063645.1 link	n.-224A>G	upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC17A8	ENST00000323346.10 link	c.763+58A>G		intron_variant	Intron 6 of 11	1	NM_139319.3	ENSP00000316909.4		Q8NDX2-1
SLC17A8	ENST00000392989.3 link	c.763+58A>G		intron_variant	Intron 6 of 10	1		ENSP00000376715.3		Q8NDX2-2

Frequencies

GnomAD3 genomes

AF:

0.293

AC:

44471

AN:

151916

Hom.:

7344

Cov.:

show subpopulations

Gnomad AFR

AF:

0.172

Gnomad AMI

AF:

0.297

Gnomad AMR

AF:

0.265

Gnomad ASJ

AF:

0.396

Gnomad EAS

AF:

0.0503

Gnomad SAS

AF:

0.236

Gnomad FIN

AF:

0.434

Gnomad MID

AF:

0.342

Gnomad NFE

AF:

0.367

Gnomad OTH

AF:

0.314

GnomAD4 exome

AF:

0.336

AC:

408170

AN:

1214914

Hom.:

73525

AF XY:

0.335

AC XY:

206679

AN XY:

616604

show subpopulations

Gnomad4 AFR exome

AF:

0.164

Gnomad4 AMR exome

AF:

0.198

Gnomad4 ASJ exome

AF:

0.390

Gnomad4 EAS exome

AF:

0.0564

Gnomad4 SAS exome

AF:

0.246

Gnomad4 FIN exome

AF:

0.436

Gnomad4 NFE exome

AF:

0.362

Gnomad4 OTH exome

AF:

0.321

GnomAD4 genome

AF:

0.293

AC:

44485

AN:

152034

Hom.:

7343

Cov.:

AF XY:

0.291

AC XY:

21667

AN XY:

74332

show subpopulations

Gnomad4 AFR

AF:

0.172

Gnomad4 AMR

AF:

0.264

Gnomad4 ASJ

AF:

0.396

Gnomad4 EAS

AF:

0.0504

Gnomad4 SAS

AF:

0.236

Gnomad4 FIN

AF:

0.434

Gnomad4 NFE

AF:

0.367

Gnomad4 OTH

AF:

0.314

Alfa

AF:

0.280

Hom.:

1684

Bravo

AF:

0.274

Asia WGS

AF:

0.155

AC:

540

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 24, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

1.1

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