rs893006

Positions:

• chr11-64598324-C-A

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.831-192C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.608 in 151,996 control chromosomes in the GnomAD database, including 28,982 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.61 (28982 hom., cov: 33)
• Consequence: SLC22A12 NM_144585.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.02

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=-0.94).
• BP6: Variant 11-64598324-C-A is Benign according to our data. Variant chr11-64598324-C-A is described in ClinVar as [Benign]. Clinvar id is 1294945.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.697 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC22A12	NM_144585.4	c.831-192C>A		intron_variant		ENST00000377574.6	NP_653186.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC22A12	ENST00000377574.6	c.831-192C>A		intron_variant		1	NM_144585.4	ENSP00000366797.1

Frequencies

GnomAD3 genomes AF: 0.608 AC: 92365 AN: 151878 Hom.: 28977 Cov.: 33

Gnomad AFR AF: 0.523

Gnomad AMI AF: 0.836

Gnomad AMR AF: 0.545

Gnomad ASJ AF: 0.718

Gnomad EAS AF: 0.224

Gnomad SAS AF: 0.575

Gnomad FIN AF: 0.572

Gnomad MID AF: 0.661

Gnomad NFE AF: 0.702

Gnomad OTH AF: 0.632

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

GnomAD4 genome AF: 0.608 AC: 92408 AN: 151996 Hom.: 28982 Cov.: 33 AF XY: 0.598 AC XY: 44444 AN XY: 74292

Gnomad4 AFR AF: 0.522

Gnomad4 AMR AF: 0.544

Gnomad4 ASJ AF: 0.718

Gnomad4 EAS AF: 0.224

Gnomad4 SAS AF: 0.575

Gnomad4 FIN AF: 0.572

Gnomad4 NFE AF: 0.702

Gnomad4 OTH AF: 0.633

Alfa AF: 0.688 Hom.: 31537

Bravo AF: 0.602

Asia WGS AF: 0.405 AC: 1411 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	3.7
DANN	Benign	0.41

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: rs893006; hg19: chr11-64365796;