Variant 11-64591323-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_144585.4(SLC22A12):c.-234C>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 0.0271 in 585,568 control chromosomes in the GnomAD database, including 314 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.024 ( 69 hom., cov: 33)

Exomes 𝑓: 0.028 ( 245 hom. )

Consequence

SLC22A12
NM_144585.4 5_prime_UTR

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.0410

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

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

BP6

Variant 11-64591323-C-T is Benign according to our data. Variant chr11-64591323-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 305224.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0239 (3646/152336) while in subpopulation NFE AF= 0.0358 (2436/68034). AF 95% confidence interval is 0.0346. There are 69 homozygotes in gnomad4. There are 1821 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 69 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC22A12	NM_144585.4 linkuse as main transcript	c.-234C>T		5_prime_UTR_variant	1/10	ENST00000377574.6	NP_653186.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC22A12	ENST00000377574.6 linkuse as main transcript	c.-234C>T		5_prime_UTR_variant	1/10	1	NM_144585.4	ENSP00000366797	P1	Q96S37-1

Frequencies

GnomAD3 genomes

AF:

0.0240

AC:

3647

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00685

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.00942

Gnomad ASJ

AF:

0.00547

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00704

Gnomad FIN

AF:

0.0660

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0358

Gnomad OTH

AF:

0.0115

GnomAD4 exome

AF:

0.0282

AC:

12217

AN:

433232

Hom.:

245

Cov.:

AF XY:

0.0270

AC XY:

6110

AN XY:

226268

show subpopulations

Gnomad4 AFR exome

AF:

0.00625

Gnomad4 AMR exome

AF:

0.00893

Gnomad4 ASJ exome

AF:

0.00657

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00734

Gnomad4 FIN exome

AF:

0.0632

Gnomad4 NFE exome

AF:

0.0347

Gnomad4 OTH exome

AF:

0.0251

GnomAD4 genome

AF:

0.0239

AC:

3646

AN:

152336

Hom.:

Cov.:

AF XY:

0.0244

AC XY:

1821

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.00683

Gnomad4 AMR

AF:

0.00928

Gnomad4 ASJ

AF:

0.00547

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00725

Gnomad4 FIN

AF:

0.0660

Gnomad4 NFE

AF:

0.0358

Gnomad4 OTH

AF:

0.0114

Alfa

AF:

0.0319

Hom.:

Bravo

AF:

0.0181

Asia WGS

AF:

0.00404

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 08, 2019	- -

Dalmatian hypouricemia

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

7.6

DANN

Benign

0.68

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over