11-64593233-C-T

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC22A12	NM_144585.4	c.507-172C>T		intron_variant	Intron 2 of 9	ENST00000377574.6	NP_653186.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC22A12	ENST00000377574.6	c.507-172C>T		intron_variant	Intron 2 of 9	1	NM_144585.4	ENSP00000366797.1

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

Gnomad4 AFR AF: 0.188

Gnomad4 AMR AF: 0.505

Gnomad4 ASJ AF: 0.714

Gnomad4 EAS AF: 0.222

Gnomad4 SAS AF: 0.573

Gnomad4 FIN AF: 0.571

Gnomad4 NFE AF: 0.695

Gnomad4 OTH AF: 0.555

Alfa AF: 0.583 Hom.: 4763

Bravo AF: 0.489

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.7
DANN	Benign	0.87

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

Publications

LitVar

Other links and lift over

dbSNP: rs10897518; hg19: chr11-64360705; COSMIC: COSV60573221;