rs121907893

Positions:

• chr11-64593548-C-G
• chr11-64593548-C-T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_144585.4(SLC22A12):​c.650C>G​(p.Thr217Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,792 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SLC22A12 NM_144585.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.177

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 Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.977

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC22A12	NM_144585.4	c.650C>G	p.Thr217Arg	missense_variant	3/10	ENST00000377574.6	NP_653186.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC22A12	ENST00000377574.6	c.650C>G	p.Thr217Arg	missense_variant	3/10	1	NM_144585.4	ENSP00000366797	P1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461792 Hom.: 0 Cov.: 33 AF XY: 0.00000275 AC XY: 2 AN XY: 727200

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 34

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.52
BayesDel_addAF	Uncertain	0.098	D
BayesDel_noAF	Benign	-0.10
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.64	D
Eigen	Benign	0.058
Eigen_PC	Benign	-0.074
FATHMM_MKL	Benign	0.25	N
LIST_S2	Benign	0.70	T
M_CAP	Uncertain	0.16	D
MetaRNN	Pathogenic	0.98	D
MetaSVM	Benign	-0.60	T
MutationAssessor	Uncertain	2.6	M
MutationTaster	Benign	1.0	D;D;D;D;N
PROVEAN	Uncertain	-3.4	D
REVEL	Uncertain	0.35
Sift	Benign	0.044	D
Sift4G	Uncertain	0.021	D
Polyphen		0.97	D
Vest4		0.65
MutPred		0.94		Gain of methylation at T217 (P = 0.0148);
MVP		0.85
MPC		0.92
ClinPred		0.97	D
GERP RS		3.8
Varity_R		0.94
gMVP		0.78

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.19		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: rs121907893; hg19: chr11-64361020;