11-64591814-C-T

Variant names:

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.258C>T(p.His86His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.646 in 1,611,802 control chromosomes in the GnomAD database, including 353,155 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.51 ( 23458 hom., cov: 32)

Exomes 𝑓: 0.66 ( 329697 hom. )

Consequence

SLC22A12
NM_144585.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.0810

Publications

38 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 11-64591814-C-T is Benign according to our data. Variant chr11-64591814-C-T is described in ClinVar as Benign. ClinVar VariationId is 305230.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.081 with no splicing effect.

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 rank	MANE	Protein	UniProt
SLC22A12	NM_144585.4 link	c.258C>T	p.His86His	synonymous_variant	Exon 1 of 10	ENST00000377574.6	NP_653186.2	Q96S37-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC22A12	ENST00000377574.6 link	c.258C>T	p.His86His	synonymous_variant	Exon 1 of 10	1	NM_144585.4	ENSP00000366797.1		Q96S37-1

Frequencies

GnomAD3 genomes

AF:

0.511

AC:

77661

AN:

151992

Hom.:

23461

Cov.:

show subpopulations

Gnomad AFR

AF:

0.198

Gnomad AMI

AF:

0.834

Gnomad AMR

AF:

0.505

Gnomad ASJ

AF:

0.715

Gnomad EAS

AF:

0.220

Gnomad SAS

AF:

0.573

Gnomad FIN

AF:

0.572

Gnomad MID

AF:

0.633

Gnomad NFE

AF:

0.695

Gnomad OTH

AF:

0.554

GnomAD2 exomes

AF:

0.574

AC:

142203

AN:

247646

AF XY:

0.591

show subpopulations

Gnomad AFR exome

AF:

0.189

Gnomad AMR exome

AF:

0.448

Gnomad ASJ exome

AF:

0.711

Gnomad EAS exome

AF:

0.225

Gnomad FIN exome

AF:

0.585

Gnomad NFE exome

AF:

0.701

Gnomad OTH exome

AF:

0.621

GnomAD4 exome

AF:

0.660

AC:

963709

AN:

1459692

Hom.:

329697

Cov.:

116

AF XY:

0.661

AC XY:

480096

AN XY:

726256

show subpopulations

African (AFR)

AF:

0.182

AC:

6100

AN:

33474

American (AMR)

AF:

0.452

AC:

20201

AN:

44700

Ashkenazi Jewish (ASJ)

AF:

0.709

AC:

18520

AN:

26122

East Asian (EAS)

AF:

0.202

AC:

8037

AN:

39690

South Asian (SAS)

AF:

0.593

AC:

51182

AN:

86250

European-Finnish (FIN)

AF:

0.593

AC:

30492

AN:

51418

Middle Eastern (MID)

AF:

0.653

AC:

3749

AN:

5742

European-Non Finnish (NFE)

AF:

0.708

AC:

787633

AN:

1111928

Other (OTH)

AF:

0.626

AC:

37795

AN:

60368

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

24394

48789

73183

97578

121972

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19466

38932

58398

77864

97330

<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:

0.511

AC:

77676

AN:

152110

Hom.:

23458

Cov.:

AF XY:

0.505

AC XY:

37516

AN XY:

74350

show subpopulations

African (AFR)

AF:

0.198

AC:

8210

AN:

41500

American (AMR)

AF:

0.505

AC:

7717

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.715

AC:

2481

AN:

3472

East Asian (EAS)

AF:

0.220

AC:

1136

AN:

5164

South Asian (SAS)

AF:

0.573

AC:

2764

AN:

4822

European-Finnish (FIN)

AF:

0.572

AC:

6048

AN:

10582

Middle Eastern (MID)

AF:

0.639

AC:

188

AN:

294

European-Non Finnish (NFE)

AF:

0.695

AC:

47200

AN:

67962

Other (OTH)

AF:

0.555

AC:

1173

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1607

3214

4820

6427

8034

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

666

1332

1998

2664

3330

<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:

0.526

Hom.:

7702

Bravo

AF:

0.492

Asia WGS

AF:

0.382

AC:

1329

AN:

3478

EpiCase

AF:

0.708

EpiControl

AF:

0.705

ClinVar

Significance: Benign

Submissions summary: Benign:6

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

This variant is associated with the following publications: (PMID: 16385546) -

Feb 03, 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

- -

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

- -

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.His86His 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 69.98% (45710/6532 0) of European chromosomes by the Exome Aggregation Consortium (ExAC, http://exa c.broadinstitute.org; dbSNP rs3825016). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

3.0

(source)

DANN

Benign

0.50

PhyloP100

0.081

Mutation Taster

=287/13

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over