rs5804
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Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1
The NM_001126108.2(SLC12A3):c.2598C>T(p.Gly866=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 1,613,402 control chromosomes in the GnomAD database, including 9,953 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.096 ( 890 hom., cov: 31)
Exomes 𝑓: 0.10 ( 9063 hom. )
Consequence
SLC12A3
NM_001126108.2 synonymous
NM_001126108.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.55
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -16 ACMG points.
BP6
?
Variant 16-56894607-C-T is Benign according to our data. Variant chr16-56894607-C-T is described in ClinVar as [Benign]. Clinvar id is 255887.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-56894607-C-T is described in Lovd as [Benign].
BA1
?
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.219 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC12A3 | NM_001126108.2 | c.2598C>T | p.Gly866= | synonymous_variant | 22/26 | ENST00000563236.6 | |
SLC12A3 | NM_000339.3 | c.2625C>T | p.Gly875= | synonymous_variant | 22/26 | ||
SLC12A3 | NM_001126107.2 | c.2622C>T | p.Gly874= | synonymous_variant | 22/26 | ||
SLC12A3 | NM_001410896.1 | c.2595C>T | p.Gly865= | synonymous_variant | 22/26 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC12A3 | ENST00000563236.6 | c.2598C>T | p.Gly866= | synonymous_variant | 22/26 | 1 | NM_001126108.2 | A1 | |
SLC12A3 | ENST00000438926.6 | c.2625C>T | p.Gly875= | synonymous_variant | 22/26 | 1 | A1 | ||
SLC12A3 | ENST00000566786.5 | c.2622C>T | p.Gly874= | synonymous_variant | 22/26 | 1 | P4 | ||
SLC12A3 | ENST00000262502.5 | c.2595C>T | p.Gly865= | synonymous_variant | 22/26 | 5 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.0964 AC: 14652AN: 151988Hom.: 885 Cov.: 31
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GnomAD3 exomes AF: 0.126 AC: 31608AN: 251316Hom.: 2522 AF XY: 0.123 AC XY: 16740AN XY: 135818
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GnomAD4 exome AF: 0.104 AC: 151924AN: 1461296Hom.: 9063 Cov.: 32 AF XY: 0.105 AC XY: 76383AN XY: 726972
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GnomAD4 genome ? AF: 0.0964 AC: 14664AN: 152106Hom.: 890 Cov.: 31 AF XY: 0.101 AC XY: 7476AN XY: 74342
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ClinVar
Significance: Benign
Submissions summary: Benign:9
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Familial hypokalemia-hypomagnesemia Benign:4
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Jun 29, 2017 | - - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 15, 2021 | - - |
Benign, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 16, 2020 | - - |
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
not specified Benign:3
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 29, 2019 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Computational scores
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Calibrated prediction
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_DL_spliceai
Position offset: 35
Find out detailed SpliceAI scores and Pangolin per-transcript scores at