chr16-56878020-G-GTCCCTCCCTCCCTCCCTCTCTCCCTCCC

Variant names:

• chr16-56878020-G-GTCCCTCCCTCCCTCCCTCTCTCCCTCCC
• rs3217425
• NM_001126108.2:c.1096-43_1096-42insCCTCTCTCCCTCCCTCCCTCCCTCCCTC

Variant summary

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

The NM_001126108.2(SLC12A3):​c.1096-43_1096-42insCCTCTCTCCCTCCCTCCCTCCCTCCCTC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000109 in 91,376 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, 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.

• Frequency: Genomes: 𝑓 0.000011 (0 hom., cov: 26)
• Consequence: SLC12A3 NM_001126108.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.837
• Publications: 1 publications found

Genes affected

SLC12A3 (HGNC:10912): (solute carrier family 12 member 3) This gene encodes a renal thiazide-sensitive sodium-chloride cotransporter that is important for electrolyte homeostasis. This cotransporter mediates sodium and chloride reabsorption in the distal convoluted tubule. Mutations in this gene cause Gitelman syndrome, a disease similar to Bartter's syndrome, that is characterized by hypokalemic alkalosis combined with hypomagnesemia, low urinary calcium, and increased renin activity associated with normal blood pressure. This cotransporter is the target for thiazide diuretics that are used for treating high blood pressure. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

SLC12A3 Gene-Disease associations (from GenCC):

• Gitelman syndrome

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC12A3	NM_001126108.2	c.1096-43_1096-42insCCTCTCTCCCTCCCTCCCTCCCTCCCTC		intron_variant	Intron 8 of 25	ENST00000563236.6	NP_001119580.2
SLC12A3	NM_000339.3	c.1096-43_1096-42insCCTCTCTCCCTCCCTCCCTCCCTCCCTC		intron_variant	Intron 8 of 25		NP_000330.3
SLC12A3	NM_001126107.2	c.1093-43_1093-42insCCTCTCTCCCTCCCTCCCTCCCTCCCTC		intron_variant	Intron 8 of 25		NP_001119579.2
SLC12A3	NM_001410896.1	c.1093-43_1093-42insCCTCTCTCCCTCCCTCCCTCCCTCCCTC		intron_variant	Intron 8 of 25		NP_001397825.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC12A3	ENST00000563236.6	c.1096-57_1096-56insTCCCTCCCTCCCTCCCTCTCTCCCTCCC		intron_variant	Intron 8 of 25	1	NM_001126108.2	ENSP00000456149.2
SLC12A3	ENST00000438926.6	c.1096-57_1096-56insTCCCTCCCTCCCTCCCTCTCTCCCTCCC		intron_variant	Intron 8 of 25	1		ENSP00000402152.2
SLC12A3	ENST00000566786.5	c.1093-57_1093-56insTCCCTCCCTCCCTCCCTCTCTCCCTCCC		intron_variant	Intron 8 of 25	1		ENSP00000457552.1
SLC12A3	ENST00000262502.5	c.1093-57_1093-56insTCCCTCCCTCCCTCCCTCTCTCCCTCCC		intron_variant	Intron 8 of 25	5		ENSP00000262502.5

Frequencies

GnomAD3 genomes AF: 0.0000109 AC: 1 AN: 91376 Hom.: 0 Cov.: 26

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000213

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.0000109 AC: 1 AN: 91376 Hom.: 0 Cov.: 26 AF XY: 0.00 AC XY: 0 AN XY: 43022

African (AFR) AF: 0.00 AC: 0 AN: 20604

American (AMR) AF: 0.00 AC: 0 AN: 8516

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2322

East Asian (EAS) AF: 0.00 AC: 0 AN: 2912

South Asian (SAS) AF: 0.00 AC: 0 AN: 2904

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5238

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 158

European-Non Finnish (NFE) AF: 0.0000213 AC: 1 AN: 46940

Other (OTH) AF: 0.00 AC: 0 AN: 1200

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.84

Splicing

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

Other links and lift over

dbSNP: rs3217425; hg19: chr16-56911932;