NM_144585.4:c.1309T>C

Variant names:

• chr11-64600390-T-C
• rs7932775
• NM_144585.4:c.1309T>C

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.1309T>C​(p.Leu437Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.227 in 1,605,460 control chromosomes in the GnomAD database, including 49,700 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. L437L) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.33 (10860 hom., cov: 33)
  • Exomes 𝑓: 0.22 (38840 hom.)
• Consequence: SLC22A12 NM_144585.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.441
• Publications: 35 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=-0.71).
• BP6: Variant 11-64600390-T-C is Benign according to our data. Variant chr11-64600390-T-C is described in ClinVar as Benign. ClinVar VariationId is 305244.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.441 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.599 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC22A12	NM_144585.4	c.1309T>C	p.Leu437Leu	synonymous_variant	Exon 8 of 10	ENST00000377574.6	NP_653186.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC22A12	ENST00000377574.6	c.1309T>C	p.Leu437Leu	synonymous_variant	Exon 8 of 10	1	NM_144585.4	ENSP00000366797.1

Frequencies

GnomAD3 genomes AF: 0.331 AC: 50367 AN: 152034 Hom.: 10827 Cov.: 33

Gnomad AFR AF: 0.605

Gnomad AMI AF: 0.127

Gnomad AMR AF: 0.241

Gnomad ASJ AF: 0.167

Gnomad EAS AF: 0.477

Gnomad SAS AF: 0.210

Gnomad FIN AF: 0.298

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.200

Gnomad OTH AF: 0.289

GnomAD2 exomes AF: 0.260 AC: 61272 AN: 236058 AF XY: 0.249

Gnomad AFR exome AF: 0.616

Gnomad AMR exome AF: 0.240

Gnomad ASJ exome AF: 0.173

Gnomad EAS exome AF: 0.479

Gnomad FIN exome AF: 0.286

Gnomad NFE exome AF: 0.198

Gnomad OTH exome AF: 0.245

GnomAD4 exome AF: 0.216 AC: 314041 AN: 1453308 Hom.: 38840 Cov.: 34 AF XY: 0.214 AC XY: 154539 AN XY: 722840

African (AFR) AF: 0.617 AC: 20624 AN: 33444

American (AMR) AF: 0.237 AC: 10456 AN: 44160

Ashkenazi Jewish (ASJ) AF: 0.176 AC: 4557 AN: 25936

East Asian (EAS) AF: 0.477 AC: 18898 AN: 39592

South Asian (SAS) AF: 0.203 AC: 17288 AN: 85034

European-Finnish (FIN) AF: 0.277 AC: 13574 AN: 49022

Middle Eastern (MID) AF: 0.241 AC: 1387 AN: 5760

European-Non Finnish (NFE) AF: 0.192 AC: 212755 AN: 1110202

Other (OTH) AF: 0.241 AC: 14502 AN: 60158

GnomAD4 genome AF: 0.332 AC: 50444 AN: 152152 Hom.: 10860 Cov.: 33 AF XY: 0.332 AC XY: 24694 AN XY: 74380

African (AFR) AF: 0.606 AC: 25138 AN: 41516

American (AMR) AF: 0.241 AC: 3688 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.167 AC: 580 AN: 3468

East Asian (EAS) AF: 0.477 AC: 2462 AN: 5158

South Asian (SAS) AF: 0.210 AC: 1011 AN: 4816

European-Finnish (FIN) AF: 0.298 AC: 3162 AN: 10606

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.200 AC: 13623 AN: 67964

Other (OTH) AF: 0.284 AC: 601 AN: 2114

Alfa AF: 0.268 Hom.: 9954

Bravo AF: 0.341

Asia WGS AF: 0.350 AC: 1214 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Dalmatian hypouricemia Benign:2

Jul 15, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	5.6
DANN	Benign	0.53
PhyloP100		-0.44
Mutation Taster		=98/2	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7932775; hg19: chr11-64367862; COSMIC: COSV60571815;