rs2665691

Positions:

• chr11-22349710-A-G
• chr11-22349710-A-T

Variant summary

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

The NM_020346.3(SLC17A6):​c.458+6345A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.656 in 151,986 control chromosomes in the GnomAD database, including 33,323 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 0.66 (33323 hom., cov: 31)
• Consequence: SLC17A6 NM_020346.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.493

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.699 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC17A6	NM_020346.3	c.458+6345A>G		intron_variant		ENST00000263160.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC17A6	ENST00000263160.4	c.458+6345A>G		intron_variant		1	NM_020346.3	P1
SLC17A6	ENST00000534115.1	n.389+6345A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.657 AC: 99707 AN: 151868 Hom.: 33303 Cov.: 31

Gnomad AFR AF: 0.667

Gnomad AMI AF: 0.562

Gnomad AMR AF: 0.525

Gnomad ASJ AF: 0.736

Gnomad EAS AF: 0.356

Gnomad SAS AF: 0.599

Gnomad FIN AF: 0.650

Gnomad MID AF: 0.744

Gnomad NFE AF: 0.704

Gnomad OTH AF: 0.667

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

GnomAD4 genome AF: 0.656 AC: 99770 AN: 151986 Hom.: 33323 Cov.: 31 AF XY: 0.650 AC XY: 48246 AN XY: 74274

Gnomad4 AFR AF: 0.667

Gnomad4 AMR AF: 0.524

Gnomad4 ASJ AF: 0.736

Gnomad4 EAS AF: 0.356

Gnomad4 SAS AF: 0.599

Gnomad4 FIN AF: 0.650

Gnomad4 NFE AF: 0.704

Gnomad4 OTH AF: 0.670

Alfa AF: 0.689 Hom.: 46365

Bravo AF: 0.643

Asia WGS AF: 0.502 AC: 1750 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	0.18
DANN	Benign	0.60

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs2665691; hg19: chr11-22371256;