rs3217425
Your query was ambiguous. Multiple possible variants found:
- chr16-56878020-GTCCC-G
- chr16-56878020-GTCCC-GTCCCTCCCTCCCTCACTCCCTCCCTCCC
- chr16-56878020-GTCCC-GTCCCTCCC
- chr16-56878020-GTCCC-GTCCCTCCCTCCC
- chr16-56878020-GTCCC-GTCCCTCCCTCCCTCCC
- chr16-56878020-GTCCC-GTCCCTCCCTCCCTCCCTCCCTCCC
- chr16-56878020-GTCCC-GTCCCTCCCTCCCTCCCTCCCTCTCTCCCTCCC
- chr16-56878020-GTCCC-GTCCCTCCCTCCCTCCCTCTCTCCCTCCCTCCC
- chr16-56878020-GTCCC-GTCCCTCCCTCCCTCGCTCCCTCCC
Variant summary
Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2
The NM_001126108.2(SLC12A3):c.1096-46_1096-43delCCTC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000196 in 510,470 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 0.0000020 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
SLC12A3
NM_001126108.2 intron
NM_001126108.2 intron
Scores
Not classified
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 syndromeInheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
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
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| SLC12A3 | NM_001126108.2 | MANE Select | c.1096-46_1096-43delCCTC | intron | N/A | NP_001119580.2 | |||
| SLC12A3 | NM_000339.3 | c.1096-46_1096-43delCCTC | intron | N/A | NP_000330.3 | ||||
| SLC12A3 | NM_001126107.2 | c.1093-46_1093-43delCCTC | intron | N/A | NP_001119579.2 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| SLC12A3 | ENST00000563236.6 | TSL:1 MANE Select | c.1096-56_1096-53delTCCC | intron | N/A | ENSP00000456149.2 | |||
| SLC12A3 | ENST00000438926.6 | TSL:1 | c.1096-56_1096-53delTCCC | intron | N/A | ENSP00000402152.2 | |||
| SLC12A3 | ENST00000566786.5 | TSL:1 | c.1093-56_1093-53delTCCC | intron | N/A | ENSP00000457552.1 |
Frequencies
GnomAD3 genomes 0.00 AC: 0AN: 91372Hom.: 0 Cov.: 26
GnomAD3 genomes
AF:
AC:
0
AN:
91372
Hom.:
Cov.:
26
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 0.00000196 AC: 1AN: 510470Hom.: 0 AF XY: 0.00000377 AC XY: 1AN XY: 265530 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
GnomAD4 exome
AF:
AC:
1
AN:
510470
Hom.:
AF XY:
AC XY:
1
AN XY:
265530
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
0
AN:
11958
American (AMR)
AF:
AC:
0
AN:
25658
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
10426
East Asian (EAS)
AF:
AC:
0
AN:
16616
South Asian (SAS)
AF:
AC:
0
AN:
50486
European-Finnish (FIN)
AF:
AC:
0
AN:
17884
Middle Eastern (MID)
AF:
AC:
0
AN:
1630
European-Non Finnish (NFE)
AF:
AC:
0
AN:
352858
Other (OTH)
AF:
AC:
1
AN:
22954
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.275
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome 0.00 AC: 0AN: 91372Hom.: 0 Cov.: 26 AF XY: 0.00 AC XY: 0AN XY: 43020
GnomAD4 genome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
91372
Hom.:
Cov.:
26
AF XY:
AC XY:
0
AN XY:
43020
African (AFR)
AF:
AC:
0
AN:
20602
American (AMR)
AF:
AC:
0
AN:
8516
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
2322
East Asian (EAS)
AF:
AC:
0
AN:
2912
South Asian (SAS)
AF:
AC:
0
AN:
2904
European-Finnish (FIN)
AF:
AC:
0
AN:
5238
Middle Eastern (MID)
AF:
AC:
0
AN:
158
European-Non Finnish (NFE)
AF:
AC:
0
AN:
46938
Other (OTH)
AF:
AC:
0
AN:
1200
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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