rs12664474

Positions:

• chr6-25875861-A-G
• chr6-25875861-A-T

Variant summary

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

The ENST00000360657.7(SLC17A3):​c.-34+6173T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 152,120 control chromosomes in the GnomAD database, including 3,150 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 0.19 (3150 hom., cov: 32)
• Consequence: SLC17A3 ENST00000360657.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.698

Genes affected

SLC17A3 (HGNC:10931): (solute carrier family 17 member 3) The protein encoded by this gene is a voltage-driven transporter that excretes intracellular urate and organic anions from the blood into renal tubule cells. Two transcript variants encoding different isoforms have been found for this gene. The longer isoform is a plasma membrane protein with transporter activity while the shorter isoform localizes to the endoplasmic reticulum. [provided by RefSeq, Aug 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.512 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC17A3	ENST00000360657.7	c.-34+6173T>C		intron_variant		2		ENSP00000353873

Frequencies

GnomAD3 genomes AF: 0.186 AC: 28305 AN: 152002 Hom.: 3143 Cov.: 32

Gnomad AFR AF: 0.136

Gnomad AMI AF: 0.0888

Gnomad AMR AF: 0.247

Gnomad ASJ AF: 0.215

Gnomad EAS AF: 0.528

Gnomad SAS AF: 0.307

Gnomad FIN AF: 0.164

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.171

Gnomad OTH AF: 0.220

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

GnomAD4 genome AF: 0.186 AC: 28340 AN: 152120 Hom.: 3150 Cov.: 32 AF XY: 0.193 AC XY: 14389 AN XY: 74378

Gnomad4 AFR AF: 0.136

Gnomad4 AMR AF: 0.248

Gnomad4 ASJ AF: 0.215

Gnomad4 EAS AF: 0.528

Gnomad4 SAS AF: 0.306

Gnomad4 FIN AF: 0.164

Gnomad4 NFE AF: 0.171

Gnomad4 OTH AF: 0.221

Alfa AF: 0.184 Hom.: 6230

Bravo AF: 0.192

Asia WGS AF: 0.386 AC: 1339 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.26
DANN	Benign	0.45

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs12664474; hg19: chr6-25876089;