Genetic Variant SLC12A3:c.1096-43_1096-42insCCTCTCTCCCTCCCTCCCTCCCTCCCTC (chr16-56878020-G-GTCCCTCCCTCCCTCCCTCTCTCCCTCCC) – ACMG Classification: Uncertain_significance (0 pts)

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

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.837

Publications

1 publications found

Variant links:

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)

SLC12A3 links:

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ACMG classification

Classification was made for transcript

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001126108.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
SLC12A3	NM_001126108.2	MANE Select	c.1096-43_1096-42insCCTCTCTCCCTCCCTCCCTCCCTCCCTC	intron	N/A	NP_001119580.2
SLC12A3	NM_000339.3		c.1096-43_1096-42insCCTCTCTCCCTCCCTCCCTCCCTCCCTC	intron	N/A	NP_000330.3
SLC12A3	NM_001126107.2		c.1093-43_1093-42insCCTCTCTCCCTCCCTCCCTCCCTCCCTC	intron	N/A	NP_001119579.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
SLC12A3	ENST00000563236.6	TSL:1 MANE Select	c.1096-57_1096-56insTCCCTCCCTCCCTCCCTCTCTCCCTCCC	intron	N/A	ENSP00000456149.2
SLC12A3	ENST00000438926.6	TSL:1	c.1096-57_1096-56insTCCCTCCCTCCCTCCCTCTCTCCCTCCC	intron	N/A	ENSP00000402152.2
SLC12A3	ENST00000566786.5	TSL:1	c.1093-57_1093-56insTCCCTCCCTCCCTCCCTCTCTCCCTCCC	intron	N/A	ENSP00000457552.1

Frequencies

GnomAD3 genomes

AF:

0.0000109

AC:

AN:

91376

Hom.:

Cov.:

show subpopulations

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:

AN:

91376

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

43022

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

20604

American (AMR)

AF:

0.00

AC:

AN:

8516

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2322

East Asian (EAS)

AF:

0.00

AC:

AN:

2912

South Asian (SAS)

AF:

0.00

AC:

AN:

2904

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5238

Middle Eastern (MID)

AF:

0.00

AC:

AN:

158

European-Non Finnish (NFE)

AF:

0.0000213

AC:

AN:

46940

Other (OTH)

AF:

0.00

AC:

AN:

1200

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.84

Splicing

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

Publications

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16-56878020-GTCCC-GTCCCTCCCTCCCTCCCTCTCTCCCTCCCTCCC

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over