NM_144585.4:c.1253T>C

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 5 ACMG points: 5P and 0B. PM2PM5PP2

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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L418R) has been classified as Pathogenic.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

SLC22A12
NM_144585.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.850

Publications

14 publications found

Variant links:

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]

SLC22A12 Gene-Disease associations (from GenCC):

hypouricemia, renal 1
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
hereditary renal hypouricemia
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

SLC22A12 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 5 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PM5

Other missense variant is known to change same aminoacid residue: Variant chr11-64599858-T-G is described in ClinVar as [Pathogenic]. Clinvar id is 3515.Status of the report is no_assertion_criteria_provided, 0 stars.

PP2

Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 10 curated pathogenic missense variants (we use a threshold of 10). The gene has 2 curated benign missense variants. Gene score misZ: 0.37234 (below the threshold of 3.09). Trascript score misZ: 0.61926 (below the threshold of 3.09). GenCC associations: The gene is linked to hereditary renal hypouricemia, hypouricemia, renal 1.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC22A12	NM_144585.4 link	c.1253T>C	p.Leu418Pro	missense_variant	Exon 7 of 10	ENST00000377574.6	NP_653186.2	Q96S37-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC22A12	ENST00000377574.6 link	c.1253T>C	p.Leu418Pro	missense_variant	Exon 7 of 10	1	NM_144585.4	ENSP00000366797.1		Q96S37-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000404

AC:

AN:

247338

AF XY:

0.00000743

show subpopulations

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1460438

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726560

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33476

American (AMR)

AF:

0.00

AC:

AN:

44700

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26104

East Asian (EAS)

AF:

0.00

AC:

AN:

39694

South Asian (SAS)

AF:

0.0000232

AC:

AN:

86240

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52314

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111772

Other (OTH)

AF:

0.00

AC:

AN:

60372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000825

AC:

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

BayesDel_noAF

Uncertain

-0.060

CADD

Benign

(source)

DANN

Benign

0.90

DEOGEN2

Uncertain

0.72

.;D;.;.;.

Eigen

Benign

-0.41

Eigen_PC

Benign

-0.49

FATHMM_MKL

Benign

0.20

LIST_S2

Benign

0.77

.;T;T;T;T

M_CAP

Uncertain

0.14

MetaRNN

Uncertain

0.58

D;D;D;D;D

MetaSVM

Benign

-0.46

MutationAssessor

Pathogenic

3.0

.;M;.;.;.

PhyloP100

0.85

PrimateAI

Uncertain

0.61

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

GERP RS

3.6

Varity_R

0.91

gMVP

0.79

Mutation Taster

=71/29

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

NM_144585.4:c.1253T>C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over