11-64599687-GC-AT

Variant names:

• chr11-64599687-GC-AT
• NM_144585.4:c.1082_1083delGCinsAT
• SLC22A12 p.Gly361Asp

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM5 PP2

The NM_144585.4(SLC22A12):​c.1082_1083delGCinsAT​(p.Gly361Asp) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G361V) has been classified as Pathogenic.

• Frequency: Genomes: not found (cov: 25)
• Consequence: SLC22A12 NM_144585.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.78
• Publications: 0 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), PanelApp Australia
• hereditary renal hypouricemia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM5: Other missense variant is known to change same aminoacid residue: Variant chr11-64599687-G-T is described in ClinVar as Pathogenic. ClinVar VariationId is 3517.Status of the report is no_assertion_criteria_provided, 0 stars.
• PP2: Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 10 curated pathogenic missense variants (we use a threshold of 10). The gene has 2 curated benign missense variants. Gene score misZ: 0.37234 (below the threshold of 3.09). Trascript score misZ: 0.61926 (below the threshold of 3.09). GenCC associations: The gene is linked to hereditary renal hypouricemia, hypouricemia, renal 1.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144585.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC22A12	NM_144585.4	MANE Select	c.1082_1083delGCinsAT	p.Gly361Asp	missense	N/A	NP_653186.2
	SLC22A12	NM_001276326.2		c.980_981delGCinsAT	p.Gly327Asp	missense	N/A	NP_001263255.1	Q96S37-4
	SLC22A12	NM_001276327.2		c.758_759delGCinsAT	p.Gly253Asp	missense	N/A	NP_001263256.1	Q96S37-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC22A12	ENST00000377574.6	TSL:1 MANE Select	c.1082_1083delGCinsAT	p.Gly361Asp	missense	N/A	ENSP00000366797.1	Q96S37-1
	SLC22A12	ENST00000336464.7	TSL:1	c.980_981delGCinsAT	p.Gly327Asp	missense	N/A	ENSP00000336836.7	Q96S37-4
	SLC22A12	ENST00000377572.5	TSL:1	c.758_759delGCinsAT	p.Gly253Asp	missense	N/A	ENSP00000366795.1	Q96S37-2

Frequencies

GnomAD3 genomes Cov.: 25

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 25

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.8

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr11-64367159;