NM_000338.3:c.2043-9dupT

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_000338.3(SLC12A1):c.2043-9dupT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.043 in 1,528,386 control chromosomes in the GnomAD database, including 1,503 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.046 ( 184 hom., cov: 31)

Exomes 𝑓: 0.043 ( 1319 hom. )

Consequence

SLC12A1
NM_000338.3 splice_region, intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 1.46

Publications

1 publications found

Variant links:

Genes affected

SLC12A1 (HGNC:10910): (solute carrier family 12 member 1) This gene encodes a kidney-specific sodium-potassium-chloride cotransporter that is expressed on the luminal membrane of renal epithelial cells of the thick ascending limb of Henle's loop and the macula densa. It plays a key role in concentrating urine and accounts for most of the NaCl resorption. It is sensitive to such diuretics as furosemide and bumetanide. Some Bartter-like syndromes result from defects in this gene. Alternative splicing results in multiple transcript variants encoding distinct isoforms. Additional splice variants have been described but their biological validity in humans has not been experimentally proven.[provided by RefSeq, May 2010]

SLC12A1 Gene-Disease associations (from GenCC):

Bartter disease type 1
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
antenatal Bartter syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

SLC12A1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP6

Variant 15-48259183-C-CT is Benign according to our data. Variant chr15-48259183-C-CT is described in ClinVar as Benign. ClinVar VariationId is 255873.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0522 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000338.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
SLC12A1	NM_000338.3	MANE Select	c.2043-9dupT	splice_region intron	N/A	NP_000329.2
SLC12A1	NM_001184832.2		c.2043-9dupT	splice_region intron	N/A	NP_001171761.1
SLC12A1	NM_001384136.1		c.2043-9dupT	splice_region intron	N/A	NP_001371065.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
SLC12A1	ENST00000380993.8	TSL:5 MANE Select	c.2043-17_2043-16insT	intron	N/A	ENSP00000370381.3
SLC12A1	ENST00000558252.5	TSL:1	n.6166-17_6166-16insT	intron	N/A
SLC12A1	ENST00000560692.5	TSL:1	n.6182-17_6182-16insT	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0460

AC:

6982

AN:

151930

Hom.:

184

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0539

Gnomad AMI

AF:

0.0154

Gnomad AMR

AF:

0.0333

Gnomad ASJ

AF:

0.0257

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0150

Gnomad FIN

AF:

0.0485

Gnomad MID

AF:

0.00637

Gnomad NFE

AF:

0.0511

Gnomad OTH

AF:

0.0379

GnomAD2 exomes

AF:

0.0373

AC:

9234

AN:

247322

AF XY:

0.0360

show subpopulations

Gnomad AFR exome

AF:

0.0547

Gnomad AMR exome

AF:

0.0211

Gnomad ASJ exome

AF:

0.0243

Gnomad EAS exome

AF:

0.000165

Gnomad FIN exome

AF:

0.0513

Gnomad NFE exome

AF:

0.0504

Gnomad OTH exome

AF:

0.0397

GnomAD4 exome

AF:

0.0427

AC:

58747

AN:

1376338

Hom.:

1319

Cov.:

AF XY:

0.0421

AC XY:

29006

AN XY:

689638

show subpopulations

African (AFR)

AF:

0.0537

AC:

1707

AN:

31760

American (AMR)

AF:

0.0219

AC:

974

AN:

44538

Ashkenazi Jewish (ASJ)

AF:

0.0236

AC:

602

AN:

25550

East Asian (EAS)

AF:

0.000229

AC:

AN:

39240

South Asian (SAS)

AF:

0.0149

AC:

1259

AN:

84352

European-Finnish (FIN)

AF:

0.0533

AC:

2840

AN:

53290

Middle Eastern (MID)

AF:

0.0108

AC:

AN:

5536

European-Non Finnish (NFE)

AF:

0.0473

AC:

48985

AN:

1034716

Other (OTH)

AF:

0.0403

AC:

2311

AN:

57356

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

2594

5189

7783

10378

12972

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1668

3336

5004

6672

8340

<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:

0.0460

AC:

6993

AN:

152048

Hom.:

184

Cov.:

AF XY:

0.0449

AC XY:

3341

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.0540

AC:

2239

AN:

41442

American (AMR)

AF:

0.0332

AC:

508

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.0257

AC:

AN:

3464

East Asian (EAS)

AF:

0.000386

AC:

AN:

5186

South Asian (SAS)

AF:

0.0152

AC:

AN:

4810

European-Finnish (FIN)

AF:

0.0485

AC:

514

AN:

10602

Middle Eastern (MID)

AF:

0.00685

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0511

AC:

3473

AN:

67948

Other (OTH)

AF:

0.0375

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

331

663

994

1326

1657

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

140

210

280

350

<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:

0.0345

Hom.:

Bravo

AF:

0.0435

Asia WGS

AF:

0.00866

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Aug 15, 2018

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Feb 03, 2020

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.5

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over