chr11-64591814-C-T

Variant names:

• chr11-64591814-C-T
• rs3825016
• NM_144585.4:c.258C>T

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.258C>T​(p.His86His) 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 1,611,802 control chromosomes in the GnomAD database, including 353,155 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.51 (23458 hom., cov: 32)
  • Exomes 𝑓: 0.66 (329697 hom.)
• Consequence: SLC22A12 NM_144585.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.0810
• Publications: 38 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 11-64591814-C-T is Benign according to our data. Variant chr11-64591814-C-T is described in ClinVar as Benign. ClinVar VariationId is 305230.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.081 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.689 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.258C>T	p.His86His	synonymous	Exon 1 of 10	NP_653186.2
	SLC22A12	NM_001276326.2		c.258C>T	p.His86His	synonymous	Exon 1 of 10	NP_001263255.1	Q96S37-4
	SLC22A12	NM_001276327.2		c.258C>T	p.His86His	synonymous	Exon 1 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.258C>T	p.His86His	synonymous	Exon 1 of 10	ENSP00000366797.1	Q96S37-1
	SLC22A12	ENST00000336464.7	TSL:1	c.258C>T	p.His86His	synonymous	Exon 1 of 10	ENSP00000336836.7	Q96S37-4
	SLC22A12	ENST00000377572.5	TSL:1	c.258C>T	p.His86His	synonymous	Exon 1 of 8	ENSP00000366795.1	Q96S37-2

Frequencies

GnomAD3 genomes AF: 0.511 AC: 77661 AN: 151992 Hom.: 23461 Cov.: 32

Gnomad AFR AF: 0.198

Gnomad AMI AF: 0.834

Gnomad AMR AF: 0.505

Gnomad ASJ AF: 0.715

Gnomad EAS AF: 0.220

Gnomad SAS AF: 0.573

Gnomad FIN AF: 0.572

Gnomad MID AF: 0.633

Gnomad NFE AF: 0.695

Gnomad OTH AF: 0.554

GnomAD2 exomes AF: 0.574 AC: 142203 AN: 247646 AF XY: 0.591

Gnomad AFR exome AF: 0.189

Gnomad AMR exome AF: 0.448

Gnomad ASJ exome AF: 0.711

Gnomad EAS exome AF: 0.225

Gnomad FIN exome AF: 0.585

Gnomad NFE exome AF: 0.701

Gnomad OTH exome AF: 0.621

GnomAD4 exome AF: 0.660 AC: 963709 AN: 1459692 Hom.: 329697 Cov.: 116 AF XY: 0.661 AC XY: 480096 AN XY: 726256

African (AFR) AF: 0.182 AC: 6100 AN: 33474

American (AMR) AF: 0.452 AC: 20201 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.709 AC: 18520 AN: 26122

East Asian (EAS) AF: 0.202 AC: 8037 AN: 39690

South Asian (SAS) AF: 0.593 AC: 51182 AN: 86250

European-Finnish (FIN) AF: 0.593 AC: 30492 AN: 51418

Middle Eastern (MID) AF: 0.653 AC: 3749 AN: 5742

European-Non Finnish (NFE) AF: 0.708 AC: 787633 AN: 1111928

Other (OTH) AF: 0.626 AC: 37795 AN: 60368

GnomAD4 genome AF: 0.511 AC: 77676 AN: 152110 Hom.: 23458 Cov.: 32 AF XY: 0.505 AC XY: 37516 AN XY: 74350

African (AFR) AF: 0.198 AC: 8210 AN: 41500

American (AMR) AF: 0.505 AC: 7717 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.715 AC: 2481 AN: 3472

East Asian (EAS) AF: 0.220 AC: 1136 AN: 5164

South Asian (SAS) AF: 0.573 AC: 2764 AN: 4822

European-Finnish (FIN) AF: 0.572 AC: 6048 AN: 10582

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

European-Non Finnish (NFE) AF: 0.695 AC: 47200 AN: 67962

Other (OTH) AF: 0.555 AC: 1173 AN: 2112

Alfa AF: 0.526 Hom.: 7702

Bravo AF: 0.492

Asia WGS AF: 0.382 AC: 1329 AN: 3478

EpiCase AF: 0.708

EpiControl AF: 0.705

ClinVar

ClinVar submissions as Germline

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	-0.84
CADD	Benign	3.0
DANN	Benign	0.50
PhyloP100		0.081
Mutation Taster		=287/13	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: rs3825016; hg19: chr11-64359286; COSMIC: COSV60570777;