chr11-64591802-C-T

Variant names:

• chr11-64591802-C-T
• rs3825017
• NM_144585.4:c.246C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_144585.4(SLC22A12):​c.246C>T​(p.Asn82Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0139 in 1,612,494 control chromosomes in the GnomAD database, including 1,903 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.019 (249 hom., cov: 33)
  • Exomes 𝑓: 0.013 (1654 hom.)
• Consequence: SLC22A12 NM_144585.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.0890
• Publications: 25 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 11-64591802-C-T is Benign according to our data. Variant chr11-64591802-C-T is described in ClinVar as Benign. ClinVar VariationId is 305229.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.089 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.268 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144585.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC22A12	NM_144585.4	MANE Select	c.246C>T	p.Asn82Asn	synonymous	Exon 1 of 10	NP_653186.2
	SLC22A12	NM_001276326.2		c.246C>T	p.Asn82Asn	synonymous	Exon 1 of 10	NP_001263255.1
	SLC22A12	NM_001276327.2		c.246C>T	p.Asn82Asn	synonymous	Exon 1 of 8	NP_001263256.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC22A12	ENST00000377574.6	TSL:1 MANE Select	c.246C>T	p.Asn82Asn	synonymous	Exon 1 of 10	ENSP00000366797.1
	SLC22A12	ENST00000336464.7	TSL:1	c.246C>T	p.Asn82Asn	synonymous	Exon 1 of 10	ENSP00000336836.7
	SLC22A12	ENST00000377572.5	TSL:1	c.246C>T	p.Asn82Asn	synonymous	Exon 1 of 8	ENSP00000366795.1

Frequencies

GnomAD3 genomes AF: 0.0193 AC: 2931 AN: 152190 Hom.: 248 Cov.: 33

Gnomad AFR AF: 0.00487

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.0536

Gnomad ASJ AF: 0.00259

Gnomad EAS AF: 0.280

Gnomad SAS AF: 0.0106

Gnomad FIN AF: 0.0185

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00244

Gnomad OTH AF: 0.0162

GnomAD2 exomes AF: 0.0374 AC: 9283 AN: 248460 AF XY: 0.0324

Gnomad AFR exome AF: 0.00422

Gnomad AMR exome AF: 0.0917

Gnomad ASJ exome AF: 0.00409

Gnomad EAS exome AF: 0.274

Gnomad FIN exome AF: 0.0207

Gnomad NFE exome AF: 0.00284

Gnomad OTH exome AF: 0.0248

GnomAD4 exome AF: 0.0133 AC: 19459 AN: 1460186 Hom.: 1654 Cov.: 30 AF XY: 0.0125 AC XY: 9076 AN XY: 726510

African (AFR) AF: 0.00311 AC: 104 AN: 33476

American (AMR) AF: 0.0880 AC: 3934 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00448 AC: 117 AN: 26124

East Asian (EAS) AF: 0.262 AC: 10402 AN: 39694

South Asian (SAS) AF: 0.00468 AC: 404 AN: 86256

European-Finnish (FIN) AF: 0.0199 AC: 1032 AN: 51814

Middle Eastern (MID) AF: 0.00156 AC: 9 AN: 5760

European-Non Finnish (NFE) AF: 0.00201 AC: 2235 AN: 1111964

Other (OTH) AF: 0.0202 AC: 1222 AN: 60378

GnomAD4 genome AF: 0.0193 AC: 2940 AN: 152308 Hom.: 249 Cov.: 33 AF XY: 0.0216 AC XY: 1606 AN XY: 74456

African (AFR) AF: 0.00486 AC: 202 AN: 41582

American (AMR) AF: 0.0543 AC: 831 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00259 AC: 9 AN: 3472

East Asian (EAS) AF: 0.280 AC: 1443 AN: 5154

South Asian (SAS) AF: 0.0110 AC: 53 AN: 4822

European-Finnish (FIN) AF: 0.0185 AC: 196 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00244 AC: 166 AN: 68026

Other (OTH) AF: 0.0161 AC: 34 AN: 2116

Alfa AF: 0.00598 Hom.: 12

Bravo AF: 0.0226

Asia WGS AF: 0.107 AC: 370 AN: 3478

EpiCase AF: 0.00196

EpiControl AF: 0.00243

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Feb 01, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

not specified Benign:1

Mar 21, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

p.Asn82Asn in exon 1 of SLC22A12: This variant is not expected to have clinical significance because it does not alter an amino acid residue, is not located wit hin the splice consensus sequence, and has been identified in 26.81% (2266/8452) of East Asian chromosomes by the Exome Aggregation Consortium (ExAC, http://exa c.broadinstitute.org; dbSNP rs3825017).

Dalmatian hypouricemia Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.8
DANN	Benign	0.50
PhyloP100		-0.089
Mutation Taster		=281/19	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs3825017; hg19: chr11-64359274; COSMIC: COSV60573931;