NM_144585.4:c.426T>C

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_144585.4(SLC22A12):c.426T>C(p.His142His) 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 1,612,940 control chromosomes in the GnomAD database, including 353,281 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.51 ( 23360 hom., cov: 31)

Exomes 𝑓: 0.66 ( 329921 hom. )

Consequence

SLC22A12
NM_144585.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.140

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 11-64592802-T-C is Benign according to our data. Variant chr11-64592802-T-C is described in ClinVar as [Benign]. Clinvar id is 305233.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64592802-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.14 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.69 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC22A12	NM_144585.4 link	c.426T>C	p.His142His	synonymous_variant	Exon 2 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.426T>C	p.His142His	synonymous_variant	Exon 2 of 10	1	NM_144585.4	ENSP00000366797.1		Q96S37-1

Frequencies

GnomAD3 genomes

AF:

0.508

AC:

77194

AN:

151830

Hom.:

23363

Cov.:

show subpopulations

Gnomad AFR

AF:

0.188

Gnomad AMI

AF:

0.836

Gnomad AMR

AF:

0.504

Gnomad ASJ

AF:

0.714

Gnomad EAS

AF:

0.222

Gnomad SAS

AF:

0.573

Gnomad FIN

AF:

0.571

Gnomad MID

AF:

0.633

Gnomad NFE

AF:

0.695

Gnomad OTH

AF:

0.554

GnomAD3 exomes

AF:

0.573

AC:

143905

AN:

251258

Hom.:

45090

AF XY:

0.590

AC XY:

80087

AN XY:

135834

show subpopulations

Gnomad AFR exome

AF:

0.178

Gnomad AMR exome

AF:

0.447

Gnomad ASJ exome

AF:

0.711

Gnomad EAS exome

AF:

0.224

Gnomad SAS exome

AF:

0.594

Gnomad FIN exome

AF:

0.583

Gnomad NFE exome

AF:

0.701

Gnomad OTH exome

AF:

0.621

GnomAD4 exome

AF:

0.660

AC:

964170

AN:

1460992

Hom.:

329921

Cov.:

AF XY:

0.661

AC XY:

480316

AN XY:

726834

show subpopulations

Gnomad4 AFR exome

AF:

0.173

Gnomad4 AMR exome

AF:

0.452

Gnomad4 ASJ exome

AF:

0.709

Gnomad4 EAS exome

AF:

0.203

Gnomad4 SAS exome

AF:

0.593

Gnomad4 FIN exome

AF:

0.592

Gnomad4 NFE exome

AF:

0.708

Gnomad4 OTH exome

AF:

0.626

GnomAD4 genome

AF:

0.508

AC:

77202

AN:

151948

Hom.:

23360

Cov.:

AF XY:

0.502

AC XY:

37258

AN XY:

74262

show subpopulations

Gnomad4 AFR

AF:

0.188

Gnomad4 AMR

AF:

0.504

Gnomad4 ASJ

AF:

0.714

Gnomad4 EAS

AF:

0.222

Gnomad4 SAS

AF:

0.574

Gnomad4 FIN

AF:

0.571

Gnomad4 NFE

AF:

0.695

Gnomad4 OTH

AF:

0.556

Alfa

AF:

0.658

Hom.:

52950

Bravo

AF:

0.489

Asia WGS

AF:

0.381

AC:

1328

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

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

This variant is associated with the following publications: (PMID: 16385546, 20714133) -

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.His142His in exon 2 of SLC22A12: This variant is not expected to have clinical significance because it does not alter an amino acid residue, is not located wi thin the splice consensus sequence, and has been identified in 69.92% (46661/667 38) of European chromosomes by the Exome Aggregation Consortium (ExAC, http://ex ac.broadinstitute.org; dbSNP rs11231825). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

8.0

DANN

Benign

0.39

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over