11-64593233-C-T

Variant names:

• chr11-64593233-C-T
• rs10897518
• NM_144585.4:c.507-172C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_144585.4(SLC22A12):​c.507-172C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.508 in 152,230 control chromosomes in the GnomAD database, including 23,406 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.51 (23406 hom., cov: 35)
• Consequence: SLC22A12 NM_144585.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.134
• 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 11-64593233-C-T is Benign according to our data. Variant chr11-64593233-C-T is described in ClinVar as Benign. ClinVar VariationId is 1294995.Status of the report is criteria_provided_single_submitter, 1 stars.
• 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC22A12	NM_144585.4	MANE Select	c.507-172C>T		intron	N/A	NP_653186.2
	SLC22A12	NM_001276326.2		c.507-172C>T		intron	N/A	NP_001263255.1
	SLC22A12	NM_001276327.2		c.506+351C>T		intron	N/A	NP_001263256.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC22A12	ENST00000377574.6	TSL:1 MANE Select	c.507-172C>T		intron	N/A	ENSP00000366797.1
	SLC22A12	ENST00000336464.7	TSL:1	c.507-172C>T		intron	N/A	ENSP00000336836.7
	SLC22A12	ENST00000377572.5	TSL:1	c.506+351C>T		intron	N/A	ENSP00000366795.1

Frequencies

GnomAD3 genomes AF: 0.508 AC: 77321 AN: 152112 Hom.: 23409 Cov.: 35

Gnomad AFR AF: 0.188

Gnomad AMI AF: 0.834

Gnomad AMR AF: 0.505

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: 0.553

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.508 AC: 77329 AN: 152230 Hom.: 23406 Cov.: 35 AF XY: 0.502 AC XY: 37343 AN XY: 74432

African (AFR) AF: 0.188 AC: 7795 AN: 41538

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

Ashkenazi Jewish (ASJ) AF: 0.714 AC: 2477 AN: 3468

East Asian (EAS) AF: 0.222 AC: 1147 AN: 5170

South Asian (SAS) AF: 0.573 AC: 2768 AN: 4830

European-Finnish (FIN) AF: 0.571 AC: 6062 AN: 10614

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

European-Non Finnish (NFE) AF: 0.695 AC: 47239 AN: 67996

Other (OTH) AF: 0.555 AC: 1175 AN: 2116

Alfa AF: 0.630 Hom.: 45136

Bravo AF: 0.489

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.7
DANN	Benign	0.87
PhyloP100		0.13
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: rs10897518; hg19: chr11-64360705; COSMIC: COSV60573221;