11-64592802-T-C

Position:

• chr11-64592802-T-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.140

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]

ACMG classification

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/exons	MANE	Protein	UniProt
SLC22A12	NM_144585.4	c.426T>C	p.His142His	synonymous_variant	2/10	ENST00000377574.6	NP_653186.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC22A12	ENST00000377574.6	c.426T>C	p.His142His	synonymous_variant	2/10	1	NM_144585.4	ENSP00000366797.1

Frequencies

GnomAD3 genomes AF: 0.508 AC: 77194 AN: 151830 Hom.: 23363 Cov.: 31

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

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.: 46 AF XY: 0.661 AC XY: 480316 AN XY: 726834

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.: 31 AF XY: 0.502 AC XY: 37258 AN XY: 74262

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

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	This variant is associated with the following publications: (PMID: 16385546, 20714133) -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

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.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

Other links and lift over

dbSNP: rs11231825; hg19: chr11-64360274; COSMIC: COSV60571842;