rs11231825

Variant names:

• chr11-64592802-T-C
• rs11231825
• NM_144585.4:c.426T>C

Your query was ambiguous. Multiple possible variants found:

• chr11-64592802-T-C
• chr11-64592802-T-A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 64 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: PanelApp Australia, Labcorp Genetics (formerly Invitae)
• hereditary renal hypouricemia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 305233.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144585.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC22A12	NM_144585.4	MANE Select	c.426T>C	p.His142His	synonymous	Exon 2 of 10	NP_653186.2
	SLC22A12	NM_001276326.2		c.426T>C	p.His142His	synonymous	Exon 2 of 10	NP_001263255.1	Q96S37-4
	SLC22A12	NM_001276327.2		c.426T>C	p.His142His	synonymous	Exon 2 of 8	NP_001263256.1	Q96S37-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC22A12	ENST00000377574.6	TSL:1 MANE Select	c.426T>C	p.His142His	synonymous	Exon 2 of 10	ENSP00000366797.1	Q96S37-1
	SLC22A12	ENST00000336464.7	TSL:1	c.426T>C	p.His142His	synonymous	Exon 2 of 10	ENSP00000336836.7	Q96S37-4
	SLC22A12	ENST00000377572.5	TSL:1	c.426T>C	p.His142His	synonymous	Exon 2 of 8	ENSP00000366795.1	Q96S37-2

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

GnomAD2 exomes AF: 0.573 AC: 143905 AN: 251258 AF XY: 0.590

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 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

African (AFR) AF: 0.173 AC: 5786 AN: 33476

American (AMR) AF: 0.452 AC: 20199 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.709 AC: 18527 AN: 26134

East Asian (EAS) AF: 0.203 AC: 8038 AN: 39692

South Asian (SAS) AF: 0.593 AC: 51180 AN: 86240

European-Finnish (FIN) AF: 0.592 AC: 31464 AN: 53126

Middle Eastern (MID) AF: 0.653 AC: 3764 AN: 5766

European-Non Finnish (NFE) AF: 0.708 AC: 787440 AN: 1111472

Other (OTH) AF: 0.626 AC: 37772 AN: 60368

GnomAD4 genome AF: 0.508 AC: 77202 AN: 151948 Hom.: 23360 Cov.: 31 AF XY: 0.502 AC XY: 37258 AN XY: 74262

African (AFR) AF: 0.188 AC: 7777 AN: 41444

American (AMR) AF: 0.504 AC: 7695 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.714 AC: 2475 AN: 3464

East Asian (EAS) AF: 0.222 AC: 1144 AN: 5146

South Asian (SAS) AF: 0.574 AC: 2758 AN: 4808

European-Finnish (FIN) AF: 0.571 AC: 6026 AN: 10554

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

European-Non Finnish (NFE) AF: 0.695 AC: 47208 AN: 67942

Other (OTH) AF: 0.556 AC: 1170 AN: 2106

Alfa AF: 0.629 Hom.: 121922

Bravo AF: 0.489

Asia WGS AF: 0.381 AC: 1328 AN: 3478

EpiCase AF: 0.708

EpiControl AF: 0.705

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	Dalmatian hypouricemia (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	8.0
DANN	Benign	0.39
PhyloP100		-0.14
Mutation Taster		=293/7	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: rs11231825; hg19: chr11-64360274; COSMIC: COSV60571842;