11-64591133-T-C

Variant names:

• chr11-64591133-T-C
• rs559946
• ENST00000377572.5:c.-424T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000377572.5(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 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -4.17
• Publications: 13 publications found

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 Gene-Disease associations (from GenCC):

• hypouricemia, renal 1

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• hereditary renal hypouricemia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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	c.-424T>C		upstream_gene_variant		ENST00000377574.6	NP_653186.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC22A12	ENST00000377574.6	c.-424T>C		upstream_gene_variant		1	NM_144585.4	ENSP00000366797.1

Frequencies

GnomAD3 genomes AF: 0.452 AC: 68780 AN: 152070 Hom.: 17724 Cov.: 34

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.: 0 AF XY: 0.351 AC XY: 12186 AN XY: 34708

African (AFR) AF: 0.670 AC: 968 AN: 1444

American (AMR) AF: 0.494 AC: 1835 AN: 3712

Ashkenazi Jewish (ASJ) AF: 0.261 AC: 387 AN: 1484

East Asian (EAS) AF: 0.764 AC: 2490 AN: 3258

South Asian (SAS) AF: 0.384 AC: 3317 AN: 8628

European-Finnish (FIN) AF: 0.384 AC: 1316 AN: 3428

Middle Eastern (MID) AF: 0.293 AC: 68 AN: 232

European-Non Finnish (NFE) AF: 0.285 AC: 11792 AN: 41350

Other (OTH) AF: 0.324 AC: 1152 AN: 3560

GnomAD4 genome AF: 0.452 AC: 68855 AN: 152188 Hom.: 17742 Cov.: 34 AF XY: 0.461 AC XY: 34267 AN XY: 74406

African (AFR) AF: 0.675 AC: 28046 AN: 41524

American (AMR) AF: 0.478 AC: 7313 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.287 AC: 994 AN: 3468

East Asian (EAS) AF: 0.778 AC: 4028 AN: 5180

South Asian (SAS) AF: 0.427 AC: 2061 AN: 4828

European-Finnish (FIN) AF: 0.429 AC: 4544 AN: 10580

Middle Eastern (MID) AF: 0.347 AC: 102 AN: 294

European-Non Finnish (NFE) AF: 0.305 AC: 20728 AN: 67988

Other (OTH) AF: 0.420 AC: 888 AN: 2114

Alfa AF: 0.394 Hom.: 12569

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

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

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) -

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
PhyloP100		-4.2
PromoterAI		0.10	Neutral
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs559946; hg19: chr11-64358605;