11-64599687-G-A

Position:

• chr11-64599687-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PM5

The ENST00000377574.6(SLC22A12):​c.1082G>A​(p.Gly361Asp) variant causes a missense change. The variant allele was found at a frequency of 0.000000686 in 1,458,778 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G361V) has been classified as Pathogenic.

• Frequency:
  • Genomes: not found (cov: 25)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: SLC22A12 ENST00000377574.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.78

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM5: Other missense variant is known to change same aminoacid residue: Variant chr11-64599687-G-T is described in ClinVar as [Pathogenic]. Clinvar id is 3517.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC22A12	NM_144585.4	c.1082G>A	p.Gly361Asp	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.1082G>A	p.Gly361Asp	missense_variant	7/10	1	NM_144585.4	ENSP00000366797	P1

Frequencies

GnomAD3 genomes Cov.: 25

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1458778 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 725770

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 25

Alfa AF: 0.0000455 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.91
BayesDel_addAF	Uncertain	0.074	D
BayesDel_noAF	Benign	-0.13
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.33	.;T;.;.;.
Eigen	Uncertain	0.67
Eigen_PC	Uncertain	0.60
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.76	.;T;T;T;T
M_CAP	Uncertain	0.10	D
MetaRNN	Uncertain	0.72	D;D;D;D;D
MetaSVM	Uncertain	-0.10	T
MutationAssessor	Pathogenic	2.9	.;M;.;.;.
MutationTaster	Benign	0.91	D;D;D;D;D
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-2.6	D;D;D;N;D
REVEL	Uncertain	0.34
Sift	Benign	0.12	T;T;T;T;T
Sift4G	Benign	0.20	T;T;T;T;T
Polyphen		1.0	D;D;D;.;.
Vest4		0.59
MutPred		0.56		.;Gain of helix (P = 0.0854);.;.;.;
MVP		0.84
MPC		1.0
ClinPred		0.99	D
GERP RS		3.8
Varity_R		0.81
gMVP		0.79

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.20		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.20		Position offset: 35

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs121907897; hg19: chr11-64367159;