Variant chr12-100380969-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_139319.3(SLC17A8):c.354+16T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00399 in 1,613,734 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0037 ( 1 hom., cov: 31)

Exomes 𝑓: 0.0040 ( 14 hom. )

Consequence

SLC17A8
NM_139319.3 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.594

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 12-100380969-T-C is Benign according to our data. Variant chr12-100380969-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 262468.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 560 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC17A8	NM_139319.3 linkuse as main transcript	c.354+16T>C		intron_variant		ENST00000323346.10	NP_647480.1
SLC17A8	NM_001145288.2 linkuse as main transcript	c.354+16T>C		intron_variant			NP_001138760.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC17A8	ENST00000323346.10 linkuse as main transcript	c.354+16T>C		intron_variant		1	NM_139319.3	ENSP00000316909	P1	Q8NDX2-1
SLC17A8	ENST00000392989.3 linkuse as main transcript	c.354+16T>C		intron_variant		1		ENSP00000376715		Q8NDX2-2

Frequencies

GnomAD3 genomes

AF:

0.00367

AC:

559

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00432

Gnomad AMI

AF:

0.0165

Gnomad AMR

AF:

0.00183

Gnomad ASJ

AF:

0.00346

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00264

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00410

Gnomad OTH

AF:

0.00383

GnomAD3 exomes

AF:

0.00306

AC:

767

AN:

251028

Hom.:

AF XY:

0.00301

AC XY:

408

AN XY:

135698

show subpopulations

Gnomad AFR exome

AF:

0.00468

Gnomad AMR exome

AF:

0.00168

Gnomad ASJ exome

AF:

0.00208

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00150

Gnomad FIN exome

AF:

0.00305

Gnomad NFE exome

AF:

0.00427

Gnomad OTH exome

AF:

0.00261

GnomAD4 exome

AF:

0.00402

AC:

5877

AN:

1461446

Hom.:

Cov.:

AF XY:

0.00388

AC XY:

2818

AN XY:

727060

show subpopulations

Gnomad4 AFR exome

AF:

0.00571

Gnomad4 AMR exome

AF:

0.00208

Gnomad4 ASJ exome

AF:

0.00199

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00119

Gnomad4 FIN exome

AF:

0.00303

Gnomad4 NFE exome

AF:

0.00452

Gnomad4 OTH exome

AF:

0.00360

GnomAD4 genome

AF:

0.00368

AC:

560

AN:

152288

Hom.:

Cov.:

AF XY:

0.00342

AC XY:

255

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.00433

Gnomad4 AMR

AF:

0.00183

Gnomad4 ASJ

AF:

0.00346

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.00264

Gnomad4 NFE

AF:

0.00410

Gnomad4 OTH

AF:

0.00379

Alfa

AF:

0.00309

Hom.:

Bravo

AF:

0.00411

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 28, 2020	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 20, 2023	- -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.014

DANN

Benign

0.36

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