NM_001365088.1:c.1825-13C>T

Variant names:

Variant summary

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

The NM_001365088.1(SLC12A6):c.1825-13C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.115 in 1,441,302 control chromosomes in the GnomAD database, including 10,102 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.10 ( 894 hom., cov: 32)

Exomes 𝑓: 0.12 ( 9208 hom. )

Consequence

SLC12A6
NM_001365088.1 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.228

Publications

5 publications found

Variant links:

Genes affected

SLC12A6 (HGNC:10914): (solute carrier family 12 member 6) This gene is a member of the K-Cl cotransporter (KCC) family. K-Cl cotransporters are integral membrane proteins that lower intracellular chloride concentrations below the electrochemical equilibrium potential. The proteins encoded by this gene are activated by cell swelling induced by hypotonic conditions. Alternate splicing results in multiple transcript variants encoding different isoforms. Mutations in this gene are associated with agenesis of the corpus callosum with peripheral neuropathy. [provided by RefSeq, Jul 2008]

SLC12A6 Gene-Disease associations (from GenCC):

agenesis of the corpus callosum with peripheral neuropathy
Inheritance: AD, AR Classification: DEFINITIVE, STRONG, SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae), Orphanet
Charcot-Marie-Tooth disease, axonal, IIa 2II
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

SLC12A6 links:

LOC124903461 (HGNC:):

LOC124903461 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 15-34245416-G-A is Benign according to our data. Variant chr15-34245416-G-A is described in ClinVar as Benign. ClinVar VariationId is 159889.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.143 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC12A6	NM_001365088.1 link	c.1825-13C>T		intron_variant	Intron 14 of 25	ENST00000354181.8	NP_001352017.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC12A6	ENST00000354181.8 link	c.1825-13C>T		intron_variant	Intron 14 of 25	1	NM_001365088.1	ENSP00000346112.3		Q9UHW9-1

Frequencies

GnomAD3 genomes

AF:

0.102

AC:

15571

AN:

152086

Hom.:

895

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0784

Gnomad AMI

AF:

0.180

Gnomad AMR

AF:

0.0748

Gnomad ASJ

AF:

0.137

Gnomad EAS

AF:

0.0214

Gnomad SAS

AF:

0.153

Gnomad FIN

AF:

0.111

Gnomad MID

AF:

0.108

Gnomad NFE

AF:

0.122

Gnomad OTH

AF:

0.0837

GnomAD2 exomes

AF:

0.106

AC:

26682

AN:

251330

AF XY:

0.110

show subpopulations

Gnomad AFR exome

AF:

0.0769

Gnomad AMR exome

AF:

0.0761

Gnomad ASJ exome

AF:

0.142

Gnomad EAS exome

AF:

0.0225

Gnomad FIN exome

AF:

0.103

Gnomad NFE exome

AF:

0.119

Gnomad OTH exome

AF:

0.110

GnomAD4 exome

AF:

0.117

AC:

150571

AN:

1289098

Hom.:

9208

Cov.:

AF XY:

0.118

AC XY:

76718

AN XY:

650570

show subpopulations

African (AFR)

AF:

0.0783

AC:

2357

AN:

30120

American (AMR)

AF:

0.0766

AC:

3410

AN:

44526

Ashkenazi Jewish (ASJ)

AF:

0.139

AC:

3480

AN:

25060

East Asian (EAS)

AF:

0.0159

AC:

620

AN:

38912

South Asian (SAS)

AF:

0.149

AC:

12377

AN:

82878

European-Finnish (FIN)

AF:

0.103

AC:

5505

AN:

53346

Middle Eastern (MID)

AF:

0.143

AC:

785

AN:

5472

European-Non Finnish (NFE)

AF:

0.121

AC:

115712

AN:

954270

Other (OTH)

AF:

0.116

AC:

6325

AN:

54514

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

6200

12400

18600

24800

31000

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3880

7760

11640

15520

19400

<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:

0.102

AC:

15574

AN:

152204

Hom.:

894

Cov.:

AF XY:

0.102

AC XY:

7570

AN XY:

74402

show subpopulations

African (AFR)

AF:

0.0783

AC:

3252

AN:

41550

American (AMR)

AF:

0.0747

AC:

1142

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.137

AC:

474

AN:

3472

East Asian (EAS)

AF:

0.0210

AC:

109

AN:

5186

South Asian (SAS)

AF:

0.153

AC:

735

AN:

4816

European-Finnish (FIN)

AF:

0.111

AC:

1174

AN:

10580

Middle Eastern (MID)

AF:

0.109

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.122

AC:

8314

AN:

67998

Other (OTH)

AF:

0.0843

AC:

178

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

688

1376

2065

2753

3441

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

174

348

522

696

870

<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:

0.121

Hom.:

459

Bravo

AF:

0.0963

Asia WGS

AF:

0.0820

AC:

284

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 08, 2013

Genetic Services Laboratory, University of Chicago

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jun 05, 2021

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Agenesis of the corpus callosum with peripheral neuropathy

Benign:2

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

Jul 10, 2021

Genome-Nilou Lab

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

7.5

(source)

DANN

Benign

0.32

PhyloP100

0.23

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