rs11602903

Variant names:

• chr11-64590769-A-T
• rs11602903
• ENST00000377567.6:c.-336A>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 18 publications found

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]

SLC22A12 Gene-Disease associations (from GenCC):

• hypouricemia, renal 1

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• hereditary renal hypouricemia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000377567.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC22A12	ENST00000377567.6	TSL:5	c.-336A>T		5_prime_UTR	Exon 1 of 9	ENSP00000366790.2
	SLC22A12	ENST00000377572.5	TSL:1	c.-788A>T		upstream_gene	N/A	ENSP00000366795.1

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

African (AFR) AF: 0.0714 AC: 1 AN: 14

American (AMR) AF: 0.500 AC: 1 AN: 2

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 1 AN: 2

East Asian (EAS) AF: 0.00 AC: 0 AN: 8

South Asian (SAS) AF: 0.583 AC: 7 AN: 12

European-Finnish (FIN) AF: 0.650 AC: 13 AN: 20

Middle Eastern (MID) AF: 0.750 AC: 3 AN: 4

European-Non Finnish (NFE) AF: 0.699 AC: 274 AN: 392

Other (OTH) AF: 0.575 AC: 23 AN: 40

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

African (AFR) AF: 0.187 AC: 7744 AN: 41412

American (AMR) AF: 0.504 AC: 7696 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.714 AC: 2476 AN: 3470

East Asian (EAS) AF: 0.221 AC: 1144 AN: 5172

South Asian (SAS) AF: 0.574 AC: 2759 AN: 4810

European-Finnish (FIN) AF: 0.570 AC: 6037 AN: 10582

Middle Eastern (MID) AF: 0.639 AC: 188 AN: 294

European-Non Finnish (NFE) AF: 0.695 AC: 47170 AN: 67904

Other (OTH) AF: 0.555 AC: 1169 AN: 2106

Alfa AF: 0.595 Hom.: 3673

Bravo AF: 0.489

Asia WGS AF: 0.380 AC: 1325 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	9.3
DANN	Benign	0.66
PhyloP100		0.015
PromoterAI		-0.020	Neutral
Mutation Taster		=300/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs11602903; hg19: chr11-64358241;