rs11110349

Positions:

• chr12-100360267-C-T

Variant summary

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

The NM_139319.3(SLC17A8):​c.101+2775C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 152,088 control chromosomes in the GnomAD database, including 5,228 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 0.24 (5228 hom., cov: 32)
• Consequence: SLC17A8 NM_139319.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0420

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.38 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC17A8	NM_139319.3	c.101+2775C>T		intron_variant		ENST00000323346.10
SLC17A8	NM_001145288.2	c.101+2775C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC17A8	ENST00000323346.10	c.101+2775C>T		intron_variant		1	NM_139319.3	P1
SLC17A8	ENST00000392989.3	c.101+2775C>T		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.243 AC: 36960 AN: 151970 Hom.: 5215 Cov.: 32

Gnomad AFR AF: 0.385

Gnomad AMI AF: 0.207

Gnomad AMR AF: 0.198

Gnomad ASJ AF: 0.252

Gnomad EAS AF: 0.0440

Gnomad SAS AF: 0.115

Gnomad FIN AF: 0.133

Gnomad MID AF: 0.188

Gnomad NFE AF: 0.209

Gnomad OTH AF: 0.234

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

GnomAD4 genome AF: 0.243 AC: 37024 AN: 152088 Hom.: 5228 Cov.: 32 AF XY: 0.235 AC XY: 17482 AN XY: 74368

Gnomad4 AFR AF: 0.385

Gnomad4 AMR AF: 0.198

Gnomad4 ASJ AF: 0.252

Gnomad4 EAS AF: 0.0438

Gnomad4 SAS AF: 0.115

Gnomad4 FIN AF: 0.133

Gnomad4 NFE AF: 0.209

Gnomad4 OTH AF: 0.237

Alfa AF: 0.241 Hom.: 1084

Bravo AF: 0.255

Asia WGS AF: 0.119 AC: 413 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.0
DANN	Benign	0.13

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: rs11110349; hg19: chr12-100754045;