11-64590769-A-T

Position:

• chr11-64590769-A-T

Variant summary

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

The ENST00000377567.6(SLC22A12):​c.-336A>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 0.508 in 152,436 control chromosomes in the GnomAD database, including 23,459 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.51 (23344 hom., cov: 30)
  • Exomes 𝑓: 0.65 (115 hom.)
• Consequence: SLC22A12 ENST00000377567.6 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0150

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=-0.83).
• BP6: Variant 11-64590769-A-T is Benign according to our data. Variant chr11-64590769-A-T is described in ClinVar as [Benign]. Clinvar id is 1271610.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.689 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC22A12	ENST00000377567.6	c.-336A>T		5_prime_UTR_variant	1/9	5
SLC22A12	ENST00000377572.5			upstream_gene_variant		1

Frequencies

GnomAD3 genomes AF: 0.508 AC: 77137 AN: 151824 Hom.: 23348 Cov.: 30

Gnomad AFR AF: 0.187

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: 0.570

Gnomad MID AF: 0.633

Gnomad NFE AF: 0.695

Gnomad OTH AF: 0.553

GnomAD4 exome AF: 0.654 AC: 323 AN: 494 Hom.: 115 Cov.: 0 AF XY: 0.671 AC XY: 263 AN XY: 392

Gnomad4 AFR exome AF: 0.0714

Gnomad4 AMR exome AF: 0.500

Gnomad4 ASJ exome AF: 0.500

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.583

Gnomad4 FIN exome AF: 0.650

Gnomad4 NFE exome AF: 0.699

Gnomad4 OTH exome AF: 0.575

GnomAD4 genome AF: 0.508 AC: 77144 AN: 151942 Hom.: 23344 Cov.: 30 AF XY: 0.501 AC XY: 37234 AN XY: 74288

Gnomad4 AFR AF: 0.187

Gnomad4 AMR AF: 0.504

Gnomad4 ASJ AF: 0.714

Gnomad4 EAS AF: 0.221

Gnomad4 SAS AF: 0.574

Gnomad4 FIN AF: 0.570

Gnomad4 NFE AF: 0.695

Gnomad4 OTH AF: 0.555

Alfa AF: 0.595 Hom.: 3673

Bravo AF: 0.489

Asia WGS AF: 0.380 AC: 1325 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

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	This variant is associated with the following publications: (PMID: 16385546) -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	9.3
DANN	Benign	0.66

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11602903; hg19: chr11-64358241;