rs2593693

Variant names:

• chr11-22346755-T-C
• rs2593693
• NM_020346.3:c.458+3390T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020346.3(SLC17A6):​c.458+3390T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.301 in 150,294 control chromosomes in the GnomAD database, including 7,659 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 0.30 (7659 hom., cov: 31)
• Consequence: SLC17A6 NM_020346.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.22
• Publications: 3 publications found

Genes affected

SLC17A6 (HGNC:16703): (solute carrier family 17 member 6) Predicted to enable L-glutamate transmembrane transporter activity and neurotransmitter transmembrane transporter activity. Involved in neurotransmitter loading into synaptic vesicle. Predicted to be located in synaptic vesicle. Predicted to be active in excitatory synapse. Predicted to be integral component of synaptic vesicle membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.462 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC17A6	NM_020346.3	c.458+3390T>C		intron_variant	Intron 3 of 11	ENST00000263160.4	NP_065079.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC17A6	ENST00000263160.4	c.458+3390T>C		intron_variant	Intron 3 of 11	1	NM_020346.3	ENSP00000263160.3
SLC17A6	ENST00000534115.1	n.389+3390T>C		intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes AF: 0.301 AC: 45219 AN: 150252 Hom.: 7659 Cov.: 31

Gnomad AFR AF: 0.468

Gnomad AMI AF: 0.231

Gnomad AMR AF: 0.212

Gnomad ASJ AF: 0.166

Gnomad EAS AF: 0.304

Gnomad SAS AF: 0.260

Gnomad FIN AF: 0.235

Gnomad MID AF: 0.260

Gnomad NFE AF: 0.241

Gnomad OTH AF: 0.279

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

GnomAD4 genome AF: 0.301 AC: 45225 AN: 150294 Hom.: 7659 Cov.: 31 AF XY: 0.298 AC XY: 21862 AN XY: 73380

African (AFR) AF: 0.468 AC: 19212 AN: 41050

American (AMR) AF: 0.212 AC: 3195 AN: 15100

Ashkenazi Jewish (ASJ) AF: 0.166 AC: 574 AN: 3468

East Asian (EAS) AF: 0.303 AC: 1560 AN: 5154

South Asian (SAS) AF: 0.260 AC: 1240 AN: 4778

European-Finnish (FIN) AF: 0.235 AC: 2309 AN: 9822

Middle Eastern (MID) AF: 0.260 AC: 75 AN: 288

European-Non Finnish (NFE) AF: 0.241 AC: 16274 AN: 67638

Other (OTH) AF: 0.276 AC: 576 AN: 2086

Alfa AF: 0.256 Hom.: 22164

Bravo AF: 0.305

Asia WGS AF: 0.282 AC: 977 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.45
DANN	Benign	0.57
PhyloP100		-1.2
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: rs2593693; hg19: chr11-22368301;