rs121907895

Positions:

• chr11-64599858-T-C
• chr11-64599858-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_144585.4(SLC22A12):​c.1253T>C​(p.Leu418Pro) 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 1,460,438 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SLC22A12 NM_144585.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.850

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC22A12	NM_144585.4	c.1253T>C	p.Leu418Pro	missense_variant	7/10	ENST00000377574.6	NP_653186.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC22A12	ENST00000377574.6	c.1253T>C	p.Leu418Pro	missense_variant	7/10	1	NM_144585.4	ENSP00000366797.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000404 AC: 1 AN: 247338 Hom.: 0 AF XY: 0.00000743 AC XY: 1 AN XY: 134580

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1460438 Hom.: 0 Cov.: 36 AF XY: 0.00000138 AC XY: 1 AN XY: 726560

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000825 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.37
BayesDel_addAF	Uncertain	0.057	T
BayesDel_noAF	Uncertain	-0.060
CADD	Benign	21
DANN	Benign	0.90
DEOGEN2	Uncertain	0.72	.;D;.;.;.
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.77	.;T;T;T;T
M_CAP	Uncertain	0.14	D
MetaRNN	Uncertain	0.58	D;D;D;D;D
MetaSVM	Benign	-0.46	T
MutationAssessor	Pathogenic	3.0	.;M;.;.;.
PrimateAI	Uncertain	0.61	T
PROVEAN	Pathogenic	-5.3	D;D;D;D;D
REVEL	Uncertain	0.38
Sift	Uncertain	0.0020	D;D;D;D;D
Sift4G	Uncertain	0.036	D;D;D;T;D
Polyphen		0.98	D;B;D;.;.
Vest4		0.45
MutPred		0.74		.;Loss of stability (P = 0.1122);.;.;.;
MVP		0.78
MPC		0.56
ClinPred		0.47	T
GERP RS		3.6
Varity_R		0.91
gMVP		0.79

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: rs121907895; hg19: chr11-64367330;