NM_144585.4:c.*517G>A

Variant names:

• chr11-64602068-G-A
• rs476037
• NM_144585.4:c.*517G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_144585.4(SLC22A12):​c.*517G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 203,516 control chromosomes in the GnomAD database, including 1,950 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (1424 hom., cov: 32)
  • Exomes 𝑓: 0.12 (526 hom.)
• Consequence: SLC22A12 NM_144585.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0230
• Publications: 20 publications found

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

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.05).
• BP6: Variant 11-64602068-G-A is Benign according to our data. Variant chr11-64602068-G-A is described in ClinVar as Benign. ClinVar VariationId is 305257.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.283 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC22A12	NM_144585.4	c.*517G>A		3_prime_UTR_variant	Exon 10 of 10	ENST00000377574.6	NP_653186.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC22A12	ENST00000377574.6	c.*517G>A		3_prime_UTR_variant	Exon 10 of 10	1	NM_144585.4	ENSP00000366797.1
SLC22A12	ENST00000377572.5	c.*517G>A		3_prime_UTR_variant	Exon 8 of 8	1		ENSP00000366795.1
SLC22A12	ENST00000377567.6	c.*517G>A		3_prime_UTR_variant	Exon 9 of 9	5		ENSP00000366790.2
SLC22A12	ENST00000473690.5	c.*517G>A		3_prime_UTR_variant	Exon 10 of 10	2		ENSP00000438437.1

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18114 AN: 151820 Hom.: 1424 Cov.: 32

Gnomad AFR AF: 0.0674

Gnomad AMI AF: 0.0329

Gnomad AMR AF: 0.240

Gnomad ASJ AF: 0.150

Gnomad EAS AF: 0.295

Gnomad SAS AF: 0.209

Gnomad FIN AF: 0.127

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.134

GnomAD4 exome AF: 0.123 AC: 6342 AN: 51578 Hom.: 526 Cov.: 0 AF XY: 0.129 AC XY: 3528 AN XY: 27268

African (AFR) AF: 0.0586 AC: 106 AN: 1810

American (AMR) AF: 0.239 AC: 885 AN: 3702

Ashkenazi Jewish (ASJ) AF: 0.130 AC: 138 AN: 1060

East Asian (EAS) AF: 0.291 AC: 770 AN: 2648

South Asian (SAS) AF: 0.190 AC: 1183 AN: 6222

European-Finnish (FIN) AF: 0.0974 AC: 177 AN: 1818

Middle Eastern (MID) AF: 0.116 AC: 22 AN: 190

European-Non Finnish (NFE) AF: 0.0891 AC: 2802 AN: 31464

Other (OTH) AF: 0.0972 AC: 259 AN: 2664

GnomAD4 genome AF: 0.119 AC: 18131 AN: 151938 Hom.: 1424 Cov.: 32 AF XY: 0.127 AC XY: 9403 AN XY: 74252

African (AFR) AF: 0.0674 AC: 2794 AN: 41434

American (AMR) AF: 0.240 AC: 3659 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.150 AC: 522 AN: 3472

East Asian (EAS) AF: 0.295 AC: 1521 AN: 5154

South Asian (SAS) AF: 0.210 AC: 1010 AN: 4808

European-Finnish (FIN) AF: 0.127 AC: 1337 AN: 10554

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.102 AC: 6936 AN: 67938

Other (OTH) AF: 0.137 AC: 289 AN: 2106

Alfa AF: 0.102 Hom.: 2192

Bravo AF: 0.125

Asia WGS AF: 0.254 AC: 882 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Dalmatian hypouricemia Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	2.2
DANN	Benign	0.43
PhyloP100		-0.023
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs476037; hg19: chr11-64369540;