rs476037

Positions:

• chr11-64602068-G-A
• chr11-64602068-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_144585.4(SLC22A12):​c.*517G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 203,516 control chromosomes in the GnomAD database, including 1,950 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.12 (1424 hom., cov: 32)
  • Exomes 𝑓: 0.12 (526 hom.)
• Consequence: SLC22A12 NM_144585.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0230

Genes affected

SLC22A12 (HGNC:17989): (solute carrier family 22 member 12) The protein encoded by this gene is a member of the organic anion transporter (OAT) family, and it acts as a urate transporter to regulate urate levels in blood. This protein is an integral membrane protein primarily found in epithelial cells of the proximal tubule of the kidney. An elevated level of serum urate, hyperuricemia, is associated with increased incidences of gout, and mutations in this gene cause renal hypouricemia type 1. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2013]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.05).
• BP6: Variant 11-64602068-G-A is Benign according to our data. Variant chr11-64602068-G-A is described in ClinVar as [Benign]. Clinvar id is 305257.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.283 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC22A12	NM_144585.4	c.*517G>A		3_prime_UTR_variant	10/10	ENST00000377574.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC22A12	ENST00000377574.6	c.*517G>A		3_prime_UTR_variant	10/10	1	NM_144585.4	P1
SLC22A12	ENST00000377572.5	c.*517G>A		3_prime_UTR_variant	8/8	1
SLC22A12	ENST00000377567.6	c.*517G>A		3_prime_UTR_variant	9/9	5
SLC22A12	ENST00000473690.5	c.*517G>A		3_prime_UTR_variant	10/10	2

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18114 AN: 151820 Hom.: 1424 Cov.: 32

Gnomad AFR AF: 0.0674

Gnomad AMI AF: 0.0329

Gnomad AMR AF: 0.240

Gnomad ASJ AF: 0.150

Gnomad EAS AF: 0.295

Gnomad SAS AF: 0.209

Gnomad FIN AF: 0.127

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.134

GnomAD4 exome AF: 0.123 AC: 6342 AN: 51578 Hom.: 526 Cov.: 0 AF XY: 0.129 AC XY: 3528 AN XY: 27268

Gnomad4 AFR exome AF: 0.0586

Gnomad4 AMR exome AF: 0.239

Gnomad4 ASJ exome AF: 0.130

Gnomad4 EAS exome AF: 0.291

Gnomad4 SAS exome AF: 0.190

Gnomad4 FIN exome AF: 0.0974

Gnomad4 NFE exome AF: 0.0891

Gnomad4 OTH exome AF: 0.0972

GnomAD4 genome AF: 0.119 AC: 18131 AN: 151938 Hom.: 1424 Cov.: 32 AF XY: 0.127 AC XY: 9403 AN XY: 74252

Gnomad4 AFR AF: 0.0674

Gnomad4 AMR AF: 0.240

Gnomad4 ASJ AF: 0.150

Gnomad4 EAS AF: 0.295

Gnomad4 SAS AF: 0.210

Gnomad4 FIN AF: 0.127

Gnomad4 NFE AF: 0.102

Gnomad4 OTH AF: 0.137

Alfa AF: 0.0983 Hom.: 1159

Bravo AF: 0.125

Asia WGS AF: 0.254 AC: 882 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Dalmatian hypouricemia Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	2.2
DANN	Benign	0.43

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: rs476037; hg19: chr11-64369540;