Genetic Variant NM_144585.4:c.246C>T (chr11-64591802-C-T) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.0890

Publications

25 publications found

Variant links:

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

SLC22A12 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
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.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.0125

AC XY:

9076

AN XY:

726510

show subpopulations

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:

AN:

5760

European-Non Finnish (NFE)

AF:

0.00201

AC:

2235

AN:

1111964

Other (OTH)

AF:

0.0202

AC:

1222

AN:

60378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

1273

2546

3819

5092

6365

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

278

556

834

1112

1390

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0193

AC:

2940

AN:

152308

Hom.:

249

Cov.:

AF XY:

0.0216

AC XY:

1606

AN XY:

74456

show subpopulations

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:

AN:

3472

East Asian (EAS)

AF:

0.280

AC:

1443

AN:

5154

South Asian (SAS)

AF:

0.0110

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.0185

AC:

196

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00244

AC:

166

AN:

68026

Other (OTH)

AF:

0.0161

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

129

258

386

515

644

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

114

152

190

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00598

Hom.:

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

LINK: link

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

(source)

DANN

Benign

0.50

PhyloP100

-0.089

Mutation Taster

=281/19

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over