rs11110349

Variant names:

• chr12-100360267-C-T
• rs11110349
• NM_139319.3:c.101+2775C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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 Gene-Disease associations (from GenCC):

• nonsyndromic genetic hearing loss

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• autosomal dominant nonsyndromic hearing loss 25

  Inheritance: AD, Unknown Classification: STRONG, LIMITED Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae)
• autosomal dominant nonsyndromic hearing loss

  Inheritance: AD Classification: SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_139319.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC17A8	NM_139319.3	MANE Select	c.101+2775C>T		intron	N/A	NP_647480.1
	SLC17A8	NM_001145288.2		c.101+2775C>T		intron	N/A	NP_001138760.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC17A8	ENST00000323346.10	TSL:1 MANE Select	c.101+2775C>T		intron	N/A	ENSP00000316909.4
	SLC17A8	ENST00000392989.3	TSL:1	c.101+2775C>T		intron	N/A	ENSP00000376715.3

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

African (AFR) AF: 0.385 AC: 15960 AN: 41438

American (AMR) AF: 0.198 AC: 3027 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.252 AC: 874 AN: 3468

East Asian (EAS) AF: 0.0438 AC: 227 AN: 5188

South Asian (SAS) AF: 0.115 AC: 556 AN: 4832

European-Finnish (FIN) AF: 0.133 AC: 1407 AN: 10588

Middle Eastern (MID) AF: 0.202 AC: 59 AN: 292

European-Non Finnish (NFE) AF: 0.209 AC: 14225 AN: 67958

Other (OTH) AF: 0.237 AC: 500 AN: 2110

Alfa AF: 0.244 Hom.: 1130

Bravo AF: 0.255

Asia WGS AF: 0.119 AC: 413 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.0
DANN	Benign	0.13
PhyloP100		-0.042
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11110349; hg19: chr12-100754045;