Genetic Variant SLC22A12:c.-336A>T (chr11-64590769-A-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000377567.6(SLC22A12):c.-336A>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.508 in 152,436 control chromosomes in the GnomAD database, including 23,459 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.51 ( 23344 hom., cov: 30)

Exomes 𝑓: 0.65 ( 115 hom. )

Consequence

SLC22A12
ENST00000377567.6 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0150

Publications

18 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 11-64590769-A-T is Benign according to our data. Variant chr11-64590769-A-T is described in ClinVar as Benign. ClinVar VariationId is 1271610.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.689 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC22A12	ENST00000377567.6 link	c.-336A>T		5_prime_UTR_variant	Exon 1 of 9	5		ENSP00000366790.2		Q96S37-2
SLC22A12	ENST00000377572.5 link	c.-788A>T		upstream_gene_variant		1		ENSP00000366795.1		Q96S37-2

Frequencies

GnomAD3 genomes

AF:

0.508

AC:

77137

AN:

151824

Hom.:

23348

Cov.:

show subpopulations

Gnomad AFR

AF:

0.187

Gnomad AMI

AF:

0.834

Gnomad AMR

AF:

0.504

Gnomad ASJ

AF:

0.714

Gnomad EAS

AF:

0.221

Gnomad SAS

AF:

0.573

Gnomad FIN

AF:

0.570

Gnomad MID

AF:

0.633

Gnomad NFE

AF:

0.695

Gnomad OTH

AF:

0.553

GnomAD4 exome

AF:

0.654

AC:

323

AN:

494

Hom.:

115

Cov.:

AF XY:

0.671

AC XY:

263

AN XY:

392

show subpopulations

African (AFR)

AF:

0.0714

AC:

AN:

American (AMR)

AF:

0.500

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.500

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.583

AC:

AN:

European-Finnish (FIN)

AF:

0.650

AC:

AN:

Middle Eastern (MID)

AF:

0.750

AC:

AN:

European-Non Finnish (NFE)

AF:

0.699

AC:

274

AN:

392

Other (OTH)

AF:

0.575

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.508

AC:

77144

AN:

151942

Hom.:

23344

Cov.:

AF XY:

0.501

AC XY:

37234

AN XY:

74288

show subpopulations

African (AFR)

AF:

0.187

AC:

7744

AN:

41412

American (AMR)

AF:

0.504

AC:

7696

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.714

AC:

2476

AN:

3470

East Asian (EAS)

AF:

0.221

AC:

1144

AN:

5172

South Asian (SAS)

AF:

0.574

AC:

2759

AN:

4810

European-Finnish (FIN)

AF:

0.570

AC:

6037

AN:

10582

Middle Eastern (MID)

AF:

0.639

AC:

188

AN:

294

European-Non Finnish (NFE)

AF:

0.695

AC:

47170

AN:

67904

Other (OTH)

AF:

0.555

AC:

1169

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1555

3109

4664

6218

7773

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

662

1324

1986

2648

3310

<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:

0.595

Hom.:

3673

Bravo

AF:

0.489

Asia WGS

AF:

0.380

AC:

1325

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Nov 12, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 16385546) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

9.3

(source)

DANN

Benign

0.66

PhyloP100

0.015

PromoterAI

-0.020

Neutral

(source)

Mutation Taster

=300/0

polymorphism (auto)

(source)

Splicing

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

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over