16-56878991-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001126108.2(SLC12A3):c.1181-82C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 1,506,828 control chromosomes in the GnomAD database, including 28,048 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.18 ( 2524 hom., cov: 32)

Exomes 𝑓: 0.19 ( 25524 hom. )

Consequence

SLC12A3
NM_001126108.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.975

Publications

13 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 16-56878991-C-T is Benign according to our data. Variant chr16-56878991-C-T is described in CliVar as Benign. Clinvar id is 1233940.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-56878991-C-T is described in CliVar as Benign. Clinvar id is 1233940.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-56878991-C-T is described in CliVar as Benign. Clinvar id is 1233940.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-56878991-C-T is described in CliVar as Benign. Clinvar id is 1233940.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-56878991-C-T is described in CliVar as Benign. Clinvar id is 1233940.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-56878991-C-T is described in CliVar as Benign. Clinvar id is 1233940.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-56878991-C-T is described in CliVar as Benign. Clinvar id is 1233940.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-56878991-C-T is described in CliVar as Benign. Clinvar id is 1233940.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-56878991-C-T is described in CliVar as Benign. Clinvar id is 1233940.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-56878991-C-T is described in CliVar as Benign. Clinvar id is 1233940.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-56878991-C-T is described in CliVar as Benign. Clinvar id is 1233940.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-56878991-C-T is described in CliVar as Benign. Clinvar id is 1233940.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-56878991-C-T is described in CliVar as Benign. Clinvar id is 1233940.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-56878991-C-T is described in CliVar as Benign. Clinvar id is 1233940.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-56878991-C-T is described in CliVar as Benign. Clinvar id is 1233940.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-56878991-C-T is described in CliVar as Benign. Clinvar id is 1233940.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-56878991-C-T is described in CliVar as Benign. Clinvar id is 1233940.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-56878991-C-T is described in CliVar as Benign. Clinvar id is 1233940.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-56878991-C-T is described in CliVar as Benign. Clinvar id is 1233940.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-56878991-C-T is described in CliVar as Benign. Clinvar id is 1233940.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-56878991-C-T is described in CliVar as Benign. Clinvar id is 1233940.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-56878991-C-T is described in CliVar as Benign. Clinvar id is 1233940.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-56878991-C-T is described in CliVar as Benign. Clinvar id is 1233940.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-56878991-C-T is described in CliVar as Benign. Clinvar id is 1233940.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-56878991-C-T is described in CliVar as Benign. Clinvar id is 1233940.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-56878991-C-T is described in CliVar as Benign. Clinvar id is 1233940.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-56878991-C-T is described in CliVar as Benign. Clinvar id is 1233940.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-56878991-C-T is described in CliVar as Benign. Clinvar id is 1233940.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-56878991-C-T is described in CliVar as Benign. Clinvar id is 1233940.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.249 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
SLC12A3	NM_001126108.2 link	c.1181-82C>T	intron_variant	Intron 9 of 25	ENST00000563236.6	NP_001119580.2	P55017-1
SLC12A3	NM_000339.3 link	c.1181-82C>T	intron_variant	Intron 9 of 25		NP_000330.3	P55017-2
SLC12A3	NM_001126107.2 link	c.1178-82C>T	intron_variant	Intron 9 of 25		NP_001119579.2	P55017-3
SLC12A3	NM_001410896.1 link	c.1178-82C>T	intron_variant	Intron 9 of 25		NP_001397825.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
SLC12A3	ENST00000563236.6 link	c.1181-82C>T	intron_variant	Intron 9 of 25	1	NM_001126108.2	ENSP00000456149.2	P55017-1
SLC12A3	ENST00000438926.6 link	c.1181-82C>T	intron_variant	Intron 9 of 25	1		ENSP00000402152.2	P55017-2
SLC12A3	ENST00000566786.5 link	c.1178-82C>T	intron_variant	Intron 9 of 25	1		ENSP00000457552.1	P55017-3
SLC12A3	ENST00000262502.5 link	c.1178-82C>T	intron_variant	Intron 9 of 25	5		ENSP00000262502.5	J3QSS1

Frequencies

GnomAD3 genomes

AF:

0.177

AC:

26942

AN:

152102

Hom.:

2520

Cov.:

show subpopulations

Gnomad AFR

AF:

0.114

Gnomad AMI

AF:

0.134

Gnomad AMR

AF:

0.247

Gnomad ASJ

AF:

0.192

Gnomad EAS

AF:

0.261

Gnomad SAS

AF:

0.214

Gnomad FIN

AF:

0.202

Gnomad MID

AF:

0.203

Gnomad NFE

AF:

0.186

Gnomad OTH

AF:

0.209

GnomAD4 exome

AF:

0.193

AC:

260995

AN:

1354608

Hom.:

25524

AF XY:

0.194

AC XY:

129936

AN XY:

670716

show subpopulations

African (AFR)

AF:

0.107

AC:

3306

AN:

30834

American (AMR)

AF:

0.267

AC:

9551

AN:

35756

Ashkenazi Jewish (ASJ)

AF:

0.195

AC:

4848

AN:

24896

East Asian (EAS)

AF:

0.260

AC:

9290

AN:

35782

South Asian (SAS)

AF:

0.210

AC:

16458

AN:

78252

European-Finnish (FIN)

AF:

0.204

AC:

9762

AN:

47968

Middle Eastern (MID)

AF:

0.220

AC:

883

AN:

4010

European-Non Finnish (NFE)

AF:

0.188

AC:

195684

AN:

1040664

Other (OTH)

AF:

0.199

AC:

11213

AN:

56446

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

11617

23234

34850

46467

58084

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6920

13840

20760

27680

34600

<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

AF:

0.177

AC:

26955

AN:

152220

Hom.:

2524

Cov.:

AF XY:

0.181

AC XY:

13493

AN XY:

74408

show subpopulations

African (AFR)

AF:

0.114

AC:

4736

AN:

41542

American (AMR)

AF:

0.248

AC:

3787

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.192

AC:

666

AN:

3470

East Asian (EAS)

AF:

0.261

AC:

1350

AN:

5174

South Asian (SAS)

AF:

0.212

AC:

1023

AN:

4820

European-Finnish (FIN)

AF:

0.202

AC:

2135

AN:

10592

Middle Eastern (MID)

AF:

0.209

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.186

AC:

12634

AN:

68012

Other (OTH)

AF:

0.209

AC:

441

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1153

2306

3460

4613

5766

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

294

588

882

1176

1470

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.180

Hom.:

8592

Bravo

AF:

0.177

Asia WGS

AF:

0.236

AC:

818

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Aug 06, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.47

(source)

DANN

Benign

0.46

PhyloP100

-0.97

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over