11-64598471-T-C

Variant names:

• chr11-64598471-T-C
• rs1529909
• NM_144585.4:c.831-45T>C

Variant summary

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

The NM_144585.4(SLC22A12):​c.831-45T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.653 in 1,550,812 control chromosomes in the GnomAD database, including 347,784 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.51 (23748 hom., cov: 33)
  • Exomes 𝑓: 0.67 (324036 hom.)
• Consequence: SLC22A12 NM_144585.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -4.86
• Publications: 11 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=-0.94).
• BP6: Variant 11-64598471-T-C is Benign according to our data. Variant chr11-64598471-T-C is described in ClinVar as Benign. ClinVar VariationId is 1222614.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.696 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC22A12	NM_144585.4	c.831-45T>C		intron_variant	Intron 4 of 9	ENST00000377574.6	NP_653186.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC22A12	ENST00000377574.6	c.831-45T>C		intron_variant	Intron 4 of 9	1	NM_144585.4	ENSP00000366797.1

Frequencies

GnomAD3 genomes AF: 0.511 AC: 77720 AN: 151976 Hom.: 23751 Cov.: 33

Gnomad AFR AF: 0.186

Gnomad AMI AF: 0.834

Gnomad AMR AF: 0.509

Gnomad ASJ AF: 0.714

Gnomad EAS AF: 0.224

Gnomad SAS AF: 0.582

Gnomad FIN AF: 0.572

Gnomad MID AF: 0.633

Gnomad NFE AF: 0.701

Gnomad OTH AF: 0.557

GnomAD2 exomes AF: 0.572 AC: 87926 AN: 153752 AF XY: 0.587

Gnomad AFR exome AF: 0.169

Gnomad AMR exome AF: 0.457

Gnomad ASJ exome AF: 0.711

Gnomad EAS exome AF: 0.223

Gnomad FIN exome AF: 0.583

Gnomad NFE exome AF: 0.706

Gnomad OTH exome AF: 0.619

GnomAD4 exome AF: 0.669 AC: 935606 AN: 1398718 Hom.: 324036 Cov.: 44 AF XY: 0.669 AC XY: 461929 AN XY: 690138

African (AFR) AF: 0.169 AC: 5370 AN: 31832

American (AMR) AF: 0.460 AC: 16502 AN: 35894

Ashkenazi Jewish (ASJ) AF: 0.709 AC: 17845 AN: 25176

East Asian (EAS) AF: 0.201 AC: 7232 AN: 36064

South Asian (SAS) AF: 0.604 AC: 47852 AN: 79276

European-Finnish (FIN) AF: 0.593 AC: 28535 AN: 48160

Middle Eastern (MID) AF: 0.663 AC: 2845 AN: 4292

European-Non Finnish (NFE) AF: 0.716 AC: 772935 AN: 1080108

Other (OTH) AF: 0.630 AC: 36490 AN: 57916

GnomAD4 genome AF: 0.511 AC: 77728 AN: 152094 Hom.: 23748 Cov.: 33 AF XY: 0.505 AC XY: 37528 AN XY: 74348

African (AFR) AF: 0.186 AC: 7714 AN: 41496

American (AMR) AF: 0.508 AC: 7771 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.714 AC: 2477 AN: 3470

East Asian (EAS) AF: 0.224 AC: 1157 AN: 5166

South Asian (SAS) AF: 0.583 AC: 2809 AN: 4822

European-Finnish (FIN) AF: 0.572 AC: 6060 AN: 10596

Middle Eastern (MID) AF: 0.639 AC: 188 AN: 294

European-Non Finnish (NFE) AF: 0.701 AC: 47613 AN: 67942

Other (OTH) AF: 0.559 AC: 1180 AN: 2112

Alfa AF: 0.529 Hom.: 10821

Bravo AF: 0.492

Asia WGS AF: 0.385 AC: 1341 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

- -

Dalmatian hypouricemia Benign:1

Jul 15, 2021

Genome-Nilou Lab

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	-0.94
CADD	Benign	0.39
DANN	Benign	0.40
PhyloP100		-4.9
Mutation Taster		=100/0	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: rs1529909; hg19: chr11-64365943; COSMIC: COSV60571848;