11-64599853-A-G

Variant names:

• chr11-64599853-A-G
• rs1630320
• NM_144585.4:c.1248A>G

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.1248A>G​(p.Ala416Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.996 in 1,612,812 control chromosomes in the GnomAD database, including 800,135 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.98 (73086 hom., cov: 29)
  • Exomes 𝑓: 1.0 (727049 hom.)
• Consequence: SLC22A12 NM_144585.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -12.9
• Publications: 16 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=-1.08).
• BP6: Variant 11-64599853-A-G is Benign according to our data. Variant chr11-64599853-A-G is described in ClinVar as Benign. ClinVar VariationId is 305241.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-12.9 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.994 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC22A12	NM_144585.4	MANE Select	c.1248A>G	p.Ala416Ala	synonymous	Exon 7 of 10	NP_653186.2
	SLC22A12	NM_001276326.2		c.1146A>G	p.Ala382Ala	synonymous	Exon 7 of 10	NP_001263255.1
	SLC22A12	NM_001276327.2		c.924A>G	p.Ala308Ala	synonymous	Exon 5 of 8	NP_001263256.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC22A12	ENST00000377574.6	TSL:1 MANE Select	c.1248A>G	p.Ala416Ala	synonymous	Exon 7 of 10	ENSP00000366797.1
	SLC22A12	ENST00000336464.7	TSL:1	c.1146A>G	p.Ala382Ala	synonymous	Exon 7 of 10	ENSP00000336836.7
	SLC22A12	ENST00000377572.5	TSL:1	c.924A>G	p.Ala308Ala	synonymous	Exon 5 of 8	ENSP00000366795.1

Frequencies

GnomAD3 genomes AF: 0.980 AC: 148923 AN: 152026 Hom.: 73030 Cov.: 29

Gnomad AFR AF: 0.930

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.990

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.994

Gnomad FIN AF: 1.00

Gnomad MID AF: 1.00

Gnomad NFE AF: 1.00

Gnomad OTH AF: 0.987

GnomAD2 exomes AF: 0.994 AC: 246686 AN: 248096 AF XY: 0.996

Gnomad AFR exome AF: 0.932

Gnomad AMR exome AF: 0.996

Gnomad ASJ exome AF: 1.00

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 1.00

Gnomad NFE exome AF: 1.00

Gnomad OTH exome AF: 0.998

GnomAD4 exome AF: 0.998 AC: 1457294 AN: 1460668 Hom.: 727049 Cov.: 88 AF XY: 0.998 AC XY: 725099 AN XY: 726680

African (AFR) AF: 0.933 AC: 31231 AN: 33476

American (AMR) AF: 0.995 AC: 44476 AN: 44700

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 26106 AN: 26106

East Asian (EAS) AF: 1.00 AC: 39696 AN: 39696

South Asian (SAS) AF: 0.995 AC: 85845 AN: 86252

European-Finnish (FIN) AF: 1.00 AC: 52376 AN: 52376

Middle Eastern (MID) AF: 0.998 AC: 5752 AN: 5764

European-Non Finnish (NFE) AF: 1.00 AC: 1111723 AN: 1111918

Other (OTH) AF: 0.995 AC: 60089 AN: 60380

GnomAD4 genome AF: 0.980 AC: 149038 AN: 152144 Hom.: 73086 Cov.: 29 AF XY: 0.981 AC XY: 72951 AN XY: 74394

African (AFR) AF: 0.930 AC: 38580 AN: 41470

American (AMR) AF: 0.990 AC: 15148 AN: 15298

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 3472 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5156 AN: 5156

South Asian (SAS) AF: 0.995 AC: 4788 AN: 4814

European-Finnish (FIN) AF: 1.00 AC: 10618 AN: 10618

Middle Eastern (MID) AF: 1.00 AC: 294 AN: 294

European-Non Finnish (NFE) AF: 1.00 AC: 67987 AN: 68000

Other (OTH) AF: 0.987 AC: 2083 AN: 2110

Alfa AF: 0.996 Hom.: 19695

Bravo AF: 0.978

Asia WGS AF: 0.996 AC: 3462 AN: 3478

EpiCase AF: 1.00

EpiControl AF: 1.00

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	-1.1
CADD	Benign	0.0050
DANN	Benign	0.32
PhyloP100		-13
Mutation Taster		=98/2	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: rs1630320; hg19: chr11-64367325; COSMIC: COSV100327486;