Genetic Variant SLC22A12:c.-424T>C (chr11-64591133-T-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000377572(SLC22A12):c.-424T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.42 in 219,284 control chromosomes in the GnomAD database, including 22,467 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.45 ( 17742 hom., cov: 34)

Exomes 𝑓: 0.35 ( 4725 hom. )

Consequence

SLC22A12
ENST00000377572 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -4.17

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.0).

BP6

Variant 11-64591133-T-C is Benign according to our data. Variant chr11-64591133-T-C is described in ClinVar as [Benign]. Clinvar id is 305218.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.758 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC22A12	NM_144585.4 link	c.-424T>C		upstream_gene_variant		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.-424T>C		upstream_gene_variant		1	NM_144585.4	ENSP00000366797.1		Q96S37-1

Frequencies

GnomAD3 genomes

AF:

0.452

AC:

68780

AN:

152070

Hom.:

17724

Cov.:

show subpopulations

Gnomad AFR

AF:

0.676

Gnomad AMI

AF:

0.166

Gnomad AMR

AF:

0.478

Gnomad ASJ

AF:

0.287

Gnomad EAS

AF:

0.778

Gnomad SAS

AF:

0.427

Gnomad FIN

AF:

0.429

Gnomad MID

AF:

0.354

Gnomad NFE

AF:

0.305

Gnomad OTH

AF:

0.422

GnomAD4 exome

AF:

0.348

AC:

23325

AN:

67096

Hom.:

4725

Cov.:

AF XY:

0.351

AC XY:

12186

AN XY:

34708

show subpopulations

Gnomad4 AFR exome

AF:

0.670

Gnomad4 AMR exome

AF:

0.494

Gnomad4 ASJ exome

AF:

0.261

Gnomad4 EAS exome

AF:

0.764

Gnomad4 SAS exome

AF:

0.384

Gnomad4 FIN exome

AF:

0.384

Gnomad4 NFE exome

AF:

0.285

Gnomad4 OTH exome

AF:

0.324

GnomAD4 genome

AF:

0.452

AC:

68855

AN:

152188

Hom.:

17742

Cov.:

AF XY:

0.461

AC XY:

34267

AN XY:

74406

show subpopulations

Gnomad4 AFR

AF:

0.675

Gnomad4 AMR

AF:

0.478

Gnomad4 ASJ

AF:

0.287

Gnomad4 EAS

AF:

0.778

Gnomad4 SAS

AF:

0.427

Gnomad4 FIN

AF:

0.429

Gnomad4 NFE

AF:

0.305

Gnomad4 OTH

AF:

0.420

Alfa

AF:

0.353

Hom.:

3794

Bravo

AF:

0.467

Asia WGS

AF:

0.607

AC:

2109

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

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: 23981340) -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.045

DANN

Benign

0.33

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