rs1630320

Variant summary

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

The NM_144585.4(SLC22A12):c.1248A>G(p.Ala416=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.996 in 1,612,812 control chromosomes in the GnomAD database, including 800,135 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.98 ( 73086 hom., cov: 29)

Exomes 𝑓: 1.0 ( 727049 hom. )

Consequence

SLC22A12
NM_144585.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -12.9

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=-1.08).

BP6

Variant 11-64599853-A-G is Benign according to our data. Variant chr11-64599853-A-G is described in ClinVar as [Benign]. Clinvar id is 305241.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64599853-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-12.9 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.994 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC22A12	NM_144585.4 linkuse as main transcript	c.1248A>G	p.Ala416=	synonymous_variant	7/10	ENST00000377574.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC22A12	ENST00000377574.6 linkuse as main transcript	c.1248A>G	p.Ala416=	synonymous_variant	7/10	1	NM_144585.4	P1	Q96S37-1

Frequencies

GnomAD3 genomes

AF:

0.980

AC:

148923

AN:

152026

Hom.:

73030

Cov.:

show subpopulations

Gnomad AFR

AF:

0.930

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.990

Gnomad ASJ

AF:

1.00

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

0.994

Gnomad FIN

AF:

1.00

Gnomad MID

AF:

1.00

Gnomad NFE

AF:

1.00

Gnomad OTH

AF:

0.987

GnomAD3 exomes

AF:

0.994

AC:

246686

AN:

248096

Hom.:

122680

AF XY:

0.996

AC XY:

134300

AN XY:

134894

show subpopulations

Gnomad AFR exome

AF:

0.932

Gnomad AMR exome

AF:

0.996

Gnomad ASJ exome

AF:

1.00

Gnomad EAS exome

AF:

1.00

Gnomad SAS exome

AF:

0.995

Gnomad FIN exome

AF:

1.00

Gnomad NFE exome

AF:

1.00

Gnomad OTH exome

AF:

0.998

GnomAD4 exome

AF:

0.998

AC:

1457294

AN:

1460668

Hom.:

727049

Cov.:

AF XY:

0.998

AC XY:

725099

AN XY:

726680

show subpopulations

Gnomad4 AFR exome

AF:

0.933

Gnomad4 AMR exome

AF:

0.995

Gnomad4 ASJ exome

AF:

1.00

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

0.995

Gnomad4 FIN exome

AF:

1.00

Gnomad4 NFE exome

AF:

1.00

Gnomad4 OTH exome

AF:

0.995

GnomAD4 genome

AF:

0.980

AC:

149038

AN:

152144

Hom.:

73086

Cov.:

AF XY:

0.981

AC XY:

72951

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.930

Gnomad4 AMR

AF:

0.990

Gnomad4 ASJ

AF:

1.00

Gnomad4 EAS

AF:

1.00

Gnomad4 SAS

AF:

0.995

Gnomad4 FIN

AF:

1.00

Gnomad4 NFE

AF:

1.00

Gnomad4 OTH

AF:

0.987

Alfa

AF:

0.997

Hom.:

19340

Bravo

AF:

0.978

Asia WGS

AF:

0.996

AC:

3462

AN:

3478

EpiCase

AF:

1.00

EpiControl

AF:

1.00

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Dalmatian hypouricemia

Benign:2

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

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 20, 2019	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 21, 2016

p.Ala416Ala in exon 7 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 99.97% (64877/648 94) of European chromosomes by the Exome Aggregation Consortium (ExAC, http://ex ac.broadinstitute.org; dbSNP rs1630320). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.1

Cadd

Benign

0.0050

Dann

Benign

0.32

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