Genetic Variant SLC12A3:c.1096-54_1096-43dupCCTCCCTCCCTC (chr16-56878020-G-GTCCCTCCCTCCC) – 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.1096-54_1096-43dupCCTCCCTCCCTC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000392 in 510,538 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 0.0 ( 0 hom., cov: 26)

Exomes 𝑓: 0.0000039 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SLC12A3
NM_001126108.2 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.837

Publications

0 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	UniProt
SLC12A3	NM_001126108.2	MANE Select	c.1096-54_1096-43dupCCTCCCTCCCTC	intron	N/A	NP_001119580.2	P55017-1
SLC12A3	NM_000339.3		c.1096-54_1096-43dupCCTCCCTCCCTC	intron	N/A	NP_000330.3	P55017-2
SLC12A3	NM_001126107.2		c.1093-54_1093-43dupCCTCCCTCCCTC	intron	N/A	NP_001119579.2	P55017-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SLC12A3	ENST00000563236.6	TSL:1 MANE Select	c.1096-57_1096-56insTCCCTCCCTCCC	intron	N/A	ENSP00000456149.2	P55017-1
SLC12A3	ENST00000438926.6	TSL:1	c.1096-57_1096-56insTCCCTCCCTCCC	intron	N/A	ENSP00000402152.2	P55017-2
SLC12A3	ENST00000566786.5	TSL:1	c.1093-57_1093-56insTCCCTCCCTCCC	intron	N/A	ENSP00000457552.1	P55017-3

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

91374

Hom.:

Cov.:

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000392

AC:

AN:

510538

Hom.:

AF XY:

0.00000753

AC XY:

AN XY:

265558

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

11958

American (AMR)

AF:

0.00

AC:

AN:

25660

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

10430

East Asian (EAS)

AF:

0.00

AC:

AN:

16620

South Asian (SAS)

AF:

0.0000198

AC:

AN:

50504

European-Finnish (FIN)

AF:

0.00

AC:

AN:

17884

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1630

European-Non Finnish (NFE)

AF:

0.00000283

AC:

AN:

352898

Other (OTH)

AF:

0.00

AC:

AN:

22954

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

91374

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

43022

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:

0.00

AC:

AN:

46938

Other (OTH)

AF:

0.00

AC:

AN:

1200

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-GTCCCTCCCTCCCTCCC

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