chr16-56865278-TTG-T
Variant names:
Variant summary
Our verdict is Pathogenic. The variant received 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_001126108.2(SLC12A3):c.46_47delTG(p.Cys16GlnfsTer13) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,580 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
SLC12A3
NM_001126108.2 frameshift
NM_001126108.2 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 2.46
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: PanelApp Australia, Orphanet, Labcorp Genetics (formerly Invitae)
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 12 ACMG points.
PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 358 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 16-56865278-TTG-T is Pathogenic according to our data. Variant chr16-56865278-TTG-T is described in ClinVar as Pathogenic. ClinVar VariationId is 1459093.Status of the report is criteria_provided_single_submitter, 1 stars.
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.46_47delTG | p.Cys16GlnfsTer13 | frameshift | Exon 1 of 26 | NP_001119580.2 | P55017-1 | |
| SLC12A3 | NM_000339.3 | c.46_47delTG | p.Cys16GlnfsTer13 | frameshift | Exon 1 of 26 | NP_000330.3 | P55017-2 | ||
| SLC12A3 | NM_001126107.2 | c.46_47delTG | p.Cys16GlnfsTer13 | frameshift | Exon 1 of 26 | NP_001119579.2 | P55017-3 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| SLC12A3 | ENST00000563236.6 | TSL:1 MANE Select | c.46_47delTG | p.Cys16GlnfsTer13 | frameshift | Exon 1 of 26 | ENSP00000456149.2 | P55017-1 | |
| SLC12A3 | ENST00000438926.6 | TSL:1 | c.46_47delTG | p.Cys16GlnfsTer13 | frameshift | Exon 1 of 26 | ENSP00000402152.2 | P55017-2 | |
| SLC12A3 | ENST00000566786.5 | TSL:1 | c.46_47delTG | p.Cys16GlnfsTer13 | frameshift | Exon 1 of 26 | ENSP00000457552.1 | P55017-3 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
33
GnomAD2 exomes AF: 0.00000399 AC: 1AN: 250758 AF XY: 0.00 show subpopulations
GnomAD2 exomes
AF:
AC:
1
AN:
250758
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461580Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 727112 show subpopulations
GnomAD4 exome
AF:
AC:
1
AN:
1461580
Hom.:
AF XY:
AC XY:
0
AN XY:
727112
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33478
American (AMR)
AF:
AC:
0
AN:
44722
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26136
East Asian (EAS)
AF:
AC:
1
AN:
39700
South Asian (SAS)
AF:
AC:
0
AN:
86258
European-Finnish (FIN)
AF:
AC:
0
AN:
53120
Middle Eastern (MID)
AF:
AC:
0
AN:
5764
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1112010
Other (OTH)
AF:
AC:
0
AN:
60392
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
2
4
6
8
10
<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
GnomAD4 genome
Cov.:
33
ClinVar
ClinVar submissions
View on ClinVar Significance:Pathogenic
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
1
-
-
not provided (1)
Computational 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
You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.