rs7929627

Variant names:

• chr11-64600264-A-G
• rs7929627
• NM_144585.4:c.1286-103A>G

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.1286-103A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.234 in 927,968 control chromosomes in the GnomAD database, including 32,145 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.33 (10869 hom., cov: 33)
  • Exomes 𝑓: 0.22 (21276 hom.)
• Consequence: SLC22A12 NM_144585.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.435
• Publications: 11 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=-0.92).
• BP6: Variant 11-64600264-A-G is Benign according to our data. Variant chr11-64600264-A-G is described in ClinVar as Benign. ClinVar VariationId is 1262572.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.6 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC22A12	NM_144585.4	c.1286-103A>G		intron_variant	Intron 7 of 9	ENST00000377574.6	NP_653186.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC22A12	ENST00000377574.6	c.1286-103A>G		intron_variant	Intron 7 of 9	1	NM_144585.4	ENSP00000366797.1

Frequencies

GnomAD3 genomes AF: 0.331 AC: 50381 AN: 151988 Hom.: 10836 Cov.: 33

Gnomad AFR AF: 0.606

Gnomad AMI AF: 0.127

Gnomad AMR AF: 0.241

Gnomad ASJ AF: 0.167

Gnomad EAS AF: 0.477

Gnomad SAS AF: 0.220

Gnomad FIN AF: 0.297

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.200

Gnomad OTH AF: 0.288

GnomAD4 exome AF: 0.215 AC: 166845 AN: 775862 Hom.: 21276 AF XY: 0.213 AC XY: 86163 AN XY: 405088

African (AFR) AF: 0.597 AC: 11405 AN: 19112

American (AMR) AF: 0.236 AC: 8247 AN: 34952

Ashkenazi Jewish (ASJ) AF: 0.174 AC: 3724 AN: 21426

East Asian (EAS) AF: 0.475 AC: 15658 AN: 32930

South Asian (SAS) AF: 0.209 AC: 14023 AN: 66944

European-Finnish (FIN) AF: 0.279 AC: 9397 AN: 33696

Middle Eastern (MID) AF: 0.233 AC: 1044 AN: 4490

European-Non Finnish (NFE) AF: 0.180 AC: 94270 AN: 524496

Other (OTH) AF: 0.240 AC: 9077 AN: 37816

GnomAD4 genome AF: 0.332 AC: 50458 AN: 152106 Hom.: 10869 Cov.: 33 AF XY: 0.332 AC XY: 24693 AN XY: 74346

African (AFR) AF: 0.606 AC: 25145 AN: 41488

American (AMR) AF: 0.241 AC: 3686 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.167 AC: 580 AN: 3472

East Asian (EAS) AF: 0.477 AC: 2455 AN: 5144

South Asian (SAS) AF: 0.219 AC: 1057 AN: 4824

European-Finnish (FIN) AF: 0.297 AC: 3144 AN: 10588

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.200 AC: 13613 AN: 67972

Other (OTH) AF: 0.284 AC: 599 AN: 2110

Alfa AF: 0.317 Hom.: 1477

Bravo AF: 0.341

Asia WGS AF: 0.351 AC: 1220 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Aug 20, 2019

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	-0.92
CADD	Benign	5.8
DANN	Benign	0.53
PhyloP100		0.43
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: rs7929627; hg19: chr11-64367736; COSMIC: COSV60573756;