11-64591133-T-C

Position:

• chr11-64591133-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000377572.5(SLC22A12):​c.-424T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.42 in 219,284 control chromosomes in the GnomAD database, including 22,467 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.45 (17742 hom., cov: 34)
  • Exomes 𝑓: 0.35 (4725 hom.)
• Consequence: SLC22A12 ENST00000377572.5 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -4.17

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BP6: Variant 11-64591133-T-C is Benign according to our data. Variant chr11-64591133-T-C is described in ClinVar as [Benign]. Clinvar id is 305218.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.758 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
SLC22A12	ENST00000377572.5	c.-424T>C		5_prime_UTR_variant	1/8	1		ENSP00000366795
SLC22A12	ENST00000377567.6	c.-286-138T>C		intron_variant		5		ENSP00000366790

Frequencies

GnomAD3 genomes AF: 0.452 AC: 68780 AN: 152070 Hom.: 17724 Cov.: 34

Gnomad AFR AF: 0.676

Gnomad AMI AF: 0.166

Gnomad AMR AF: 0.478

Gnomad ASJ AF: 0.287

Gnomad EAS AF: 0.778

Gnomad SAS AF: 0.427

Gnomad FIN AF: 0.429

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.305

Gnomad OTH AF: 0.422

GnomAD4 exome AF: 0.348 AC: 23325 AN: 67096 Hom.: 4725 Cov.: 0 AF XY: 0.351 AC XY: 12186 AN XY: 34708

Gnomad4 AFR exome AF: 0.670

Gnomad4 AMR exome AF: 0.494

Gnomad4 ASJ exome AF: 0.261

Gnomad4 EAS exome AF: 0.764

Gnomad4 SAS exome AF: 0.384

Gnomad4 FIN exome AF: 0.384

Gnomad4 NFE exome AF: 0.285

Gnomad4 OTH exome AF: 0.324

GnomAD4 genome AF: 0.452 AC: 68855 AN: 152188 Hom.: 17742 Cov.: 34 AF XY: 0.461 AC XY: 34267 AN XY: 74406

Gnomad4 AFR AF: 0.675

Gnomad4 AMR AF: 0.478

Gnomad4 ASJ AF: 0.287

Gnomad4 EAS AF: 0.778

Gnomad4 SAS AF: 0.427

Gnomad4 FIN AF: 0.429

Gnomad4 NFE AF: 0.305

Gnomad4 OTH AF: 0.420

Alfa AF: 0.353 Hom.: 3794

Bravo AF: 0.467

Asia WGS AF: 0.607 AC: 2109 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	This variant is associated with the following publications: (PMID: 23981340) -

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	-1.0
CADD	Benign	0.045
DANN	Benign	0.33

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: rs559946; hg19: chr11-64358605;