dbSNP rs893006: SLC22A12:c.831-192C>A (chr11-64598324-C-A) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

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

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.02

Publications

20 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: Benign. The variant received -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 rank	MANE	Protein	UniProt
SLC22A12	NM_144585.4 link	c.831-192C>A		intron_variant	Intron 4 of 9	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.831-192C>A		intron_variant	Intron 4 of 9	1	NM_144585.4	ENSP00000366797.1		Q96S37-1

Frequencies

GnomAD3 genomes

AF:

0.608

AC:

92365

AN:

151878

Hom.:

28977

Cov.:

show subpopulations

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.:

AF XY:

0.598

AC XY:

44444

AN XY:

74292

show subpopulations

African (AFR)

AF:

0.522

AC:

21649

AN:

41436

American (AMR)

AF:

0.544

AC:

8325

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.718

AC:

2494

AN:

3472

East Asian (EAS)

AF:

0.224

AC:

1159

AN:

5176

South Asian (SAS)

AF:

0.575

AC:

2770

AN:

4816

European-Finnish (FIN)

AF:

0.572

AC:

6058

AN:

10582

Middle Eastern (MID)

AF:

0.670

AC:

197

AN:

294

European-Non Finnish (NFE)

AF:

0.702

AC:

47660

AN:

67906

Other (OTH)

AF:

0.633

AC:

1335

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1780

3561

5341

7122

8902

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

764

1528

2292

3056

3820

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.666

Hom.:

41853

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

LINK: link

Submissions by phenotype

not provided

Benign:1

Nov 12, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

3.7

(source)

DANN

Benign

0.41

PhyloP100

-1.0

Mutation Taster

=100/0

polymorphism (auto)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over