GeneBe

chr16-56878020-GTCCC-G

Variant names:

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

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)

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;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SLC12A3NM_001126108.2 linkc.1096-46_1096-43delCCTC intron_variant Intron 8 of 25 ENST00000563236.6 NP_001119580.2 P55017-1
SLC12A3NM_000339.3 linkc.1096-46_1096-43delCCTC intron_variant Intron 8 of 25 NP_000330.3 P55017-2
SLC12A3NM_001126107.2 linkc.1093-46_1093-43delCCTC intron_variant Intron 8 of 25 NP_001119579.2 P55017-3
SLC12A3NM_001410896.1 linkc.1093-46_1093-43delCCTC intron_variant Intron 8 of 25 NP_001397825.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SLC12A3ENST00000563236.6 linkc.1096-56_1096-53delTCCC intron_variant Intron 8 of 25 1 NM_001126108.2 ENSP00000456149.2 P55017-1
SLC12A3ENST00000438926.6 linkc.1096-56_1096-53delTCCC intron_variant Intron 8 of 25 1 ENSP00000402152.2 P55017-2
SLC12A3ENST00000566786.5 linkc.1093-56_1093-53delTCCC intron_variant Intron 8 of 25 1 ENSP00000457552.1 P55017-3
SLC12A3ENST00000262502.5 linkc.1093-56_1093-53delTCCC intron_variant Intron 8 of 25 5 ENSP00000262502.5 J3QSS1

Frequencies

GnomAD3 genomes
AF:
0.00
AC:
0
AN:
91372
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000196
AC:
1
AN:
510470
Hom.:
0
AF XY:
0.00000377
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:
0.00
AC:
0
AN:
11958
American (AMR)
AF:
0.00
AC:
0
AN:
25658
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
10426
East Asian (EAS)
AF:
0.00
AC:
0
AN:
16616
South Asian (SAS)
AF:
0.00
AC:
0
AN:
50486
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
17884
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
1630
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
352858
Other (OTH)
AF:
0.0000436
AC:
1
AN:
22954
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), 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
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
91372
Hom.:
0
Cov.:
26
AF XY:
0.00
AC XY:
0
AN XY:
43020
African (AFR)
AF:
0.00
AC:
0
AN:
20602
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:
0.00
AC:
0
AN:
46938
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

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

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

Publications

Other links and lift over

dbSNP: rs3217425; hg19: chr16-56911932; API