Variant rs3825016 details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000377574.6(SLC22A12):c.258C>T(p.His86=) 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
ENST00000377574.6 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.0810

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 305230.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64591814-C-T is described in Lovd as [Benign].

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/exons	MANE	Protein	UniProt
SLC22A12	NM_144585.4 linkuse as main transcript	c.258C>T	p.His86=	synonymous_variant	1/10	ENST00000377574.6	NP_653186.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC22A12	ENST00000377574.6 linkuse as main transcript	c.258C>T	p.His86=	synonymous_variant	1/10	1	NM_144585.4	ENSP00000366797	P1	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

GnomAD3 exomes

AF:

0.574

AC:

142203

AN:

247646

Hom.:

44559

AF XY:

0.591

AC XY:

79427

AN XY:

134478

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 SAS exome

AF:

0.594

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

Gnomad4 AFR exome

AF:

0.182

Gnomad4 AMR exome

AF:

0.452

Gnomad4 ASJ exome

AF:

0.709

Gnomad4 EAS exome

AF:

0.202

Gnomad4 SAS exome

AF:

0.593

Gnomad4 FIN exome

AF:

0.593

Gnomad4 NFE exome

AF:

0.708

Gnomad4 OTH exome

AF:

0.626

GnomAD4 genome

AF:

0.511

AC:

77676

AN:

152110

Hom.:

23458

Cov.:

AF XY:

0.505

AC XY:

37516

AN XY:

74350

show subpopulations

Gnomad4 AFR

AF:

0.198

Gnomad4 AMR

AF:

0.505

Gnomad4 ASJ

AF:

0.715

Gnomad4 EAS

AF:

0.220

Gnomad4 SAS

AF:

0.573

Gnomad4 FIN

AF:

0.572

Gnomad4 NFE

AF:

0.695

Gnomad4 OTH

AF:

0.555

Alfa

AF:

0.532

Hom.:

7688

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

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	This variant is associated with the following publications: (PMID: 16385546) -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Dalmatian hypouricemia

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 15, 2021	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 21, 2016

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

DANN

Benign

0.50

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