11-64590839-C-T

Position:

• chr11-64590839-C-T

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.-718C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.511 in 152,498 control chromosomes in the GnomAD database, including 23,574 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.51 (23450 hom., cov: 32)
  • Exomes 𝑓: 0.69 (124 hom.)
• Consequence: SLC22A12 ENST00000377572.5 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -3.24

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=-0.89).
• BP6: Variant 11-64590839-C-T is Benign according to our data. Variant chr11-64590839-C-T is described in ClinVar as [Benign]. Clinvar id is 305213.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.69 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.-718C>T		5_prime_UTR_variant	1/8	1		ENSP00000366795
SLC22A12	ENST00000377567.6	c.-287+21C>T		intron_variant		5		ENSP00000366790

Frequencies

GnomAD3 genomes AF: 0.511 AC: 77621 AN: 151886 Hom.: 23453 Cov.: 32

Gnomad AFR AF: 0.198

Gnomad AMI AF: 0.834

Gnomad AMR AF: 0.504

Gnomad ASJ AF: 0.714

Gnomad EAS AF: 0.221

Gnomad SAS AF: 0.573

Gnomad FIN AF: 0.571

Gnomad MID AF: 0.633

Gnomad NFE AF: 0.695

Gnomad OTH AF: 0.556

GnomAD4 exome AF: 0.691 AC: 340 AN: 492 Hom.: 124 Cov.: 0 AF XY: 0.675 AC XY: 239 AN XY: 354

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.375

Gnomad4 ASJ exome AF: 1.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.400

Gnomad4 FIN exome AF: 0.700

Gnomad4 NFE exome AF: 0.709

Gnomad4 OTH exome AF: 0.750

GnomAD4 genome AF: 0.511 AC: 77636 AN: 152006 Hom.: 23450 Cov.: 32 AF XY: 0.504 AC XY: 37467 AN XY: 74272

Gnomad4 AFR AF: 0.197

Gnomad4 AMR AF: 0.504

Gnomad4 ASJ AF: 0.714

Gnomad4 EAS AF: 0.221

Gnomad4 SAS AF: 0.573

Gnomad4 FIN AF: 0.571

Gnomad4 NFE AF: 0.695

Gnomad4 OTH AF: 0.557

Alfa AF: 0.670 Hom.: 41065

Bravo AF: 0.492

Asia WGS AF: 0.381 AC: 1327 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	clinical testing	GeneDx	Nov 12, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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	-0.89
CADD	Benign	0.41
DANN	Benign	0.54

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs9734313; hg19: chr11-64358311;