12-100380391-A-G

Position:

• chr12-100380391-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_139319.3(SLC17A8):​c.102-310A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.64 in 151,546 control chromosomes in the GnomAD database, including 32,876 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.64 (32876 hom., cov: 29)
• Consequence: SLC17A8 NM_139319.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.233

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 12-100380391-A-G is Benign according to our data. Variant chr12-100380391-A-G is described in ClinVar as [Benign]. Clinvar id is 1225423.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.971 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC17A8	NM_139319.3	c.102-310A>G		intron_variant		ENST00000323346.10	NP_647480.1
SLC17A8	NM_001145288.2	c.102-310A>G		intron_variant			NP_001138760.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC17A8	ENST00000323346.10	c.102-310A>G		intron_variant		1	NM_139319.3	ENSP00000316909	P1
SLC17A8	ENST00000392989.3	c.102-310A>G		intron_variant		1		ENSP00000376715

Frequencies

GnomAD3 genomes AF: 0.640 AC: 96897 AN: 151430 Hom.: 32837 Cov.: 29

Gnomad AFR AF: 0.828

Gnomad AMI AF: 0.532

Gnomad AMR AF: 0.671

Gnomad ASJ AF: 0.529

Gnomad EAS AF: 0.994

Gnomad SAS AF: 0.707

Gnomad FIN AF: 0.593

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.502

Gnomad OTH AF: 0.622

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.640 AC: 96995 AN: 151546 Hom.: 32876 Cov.: 29 AF XY: 0.647 AC XY: 47867 AN XY: 74022

Gnomad4 AFR AF: 0.828

Gnomad4 AMR AF: 0.671

Gnomad4 ASJ AF: 0.529

Gnomad4 EAS AF: 0.994

Gnomad4 SAS AF: 0.706

Gnomad4 FIN AF: 0.593

Gnomad4 NFE AF: 0.502

Gnomad4 OTH AF: 0.622

Alfa AF: 0.479 Hom.: 2729

Bravo AF: 0.657

Asia WGS AF: 0.834 AC: 2899 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.9
DANN	Benign	0.74

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

Other links and lift over

dbSNP: rs943403; hg19: chr12-100774169;