rs10778050

chr12-100375049-G-Achr12-100375049-G-Cchr12-100375049-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_139319.3(SLC17A8):c.102-5652G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.543 in 150,450 control chromosomes in the GnomAD database, including 22,733 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.54 (22733 hom., cov: 27)
• Consequence: SLC17A8 NM_139319.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.14

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.847 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC17A8	NM_139319.3	c.102-5652G>A		intron_variant		ENST00000323346.10
SLC17A8	NM_001145288.2	c.102-5652G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC17A8	ENST00000323346.10	c.102-5652G>A		intron_variant		1	NM_139319.3	P1
SLC17A8	ENST00000392989.3	c.102-5652G>A		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.543 AC: 81577 AN: 150332 Hom.: 22721 Cov.: 27

Gnomad AFR AF: 0.561

Gnomad AMI AF: 0.463

Gnomad AMR AF: 0.621

Gnomad ASJ AF: 0.505

Gnomad EAS AF: 0.868

Gnomad SAS AF: 0.699

Gnomad FIN AF: 0.534

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.483

Gnomad OTH AF: 0.541

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

GnomAD4 genome AF: 0.543 AC: 81633 AN: 150450 Hom.: 22733 Cov.: 27 AF XY: 0.550 AC XY: 40357 AN XY: 73372

Gnomad4 AFR AF: 0.560

Gnomad4 AMR AF: 0.622

Gnomad4 ASJ AF: 0.505

Gnomad4 EAS AF: 0.868

Gnomad4 SAS AF: 0.698

Gnomad4 FIN AF: 0.534

Gnomad4 NFE AF: 0.483

Gnomad4 OTH AF: 0.540

Alfa AF: 0.498 Hom.: 32557

Bravo AF: 0.551

Asia WGS AF: 0.753 AC: 2616 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	3.0
Dann	Benign	0.48

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: rs10778050; hg19: chr12-100768827;