rs7164902

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001365088.1(SLC12A6):c.475C>T(p.Leu159Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.244 in 1,611,736 control chromosomes in the GnomAD database, including 48,847 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. L159L) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.23 ( 4240 hom., cov: 32)

Exomes 𝑓: 0.24 ( 44607 hom. )

Consequence

SLC12A6
NM_001365088.1 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: 1.68

Publications

25 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.45).

BP6

Variant 15-34258881-G-A is Benign according to our data. Variant chr15-34258881-G-A is described in ClinVar as [Benign]. Clinvar id is 159898.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.68 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.333 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC12A6	NM_001365088.1 link	c.475C>T	p.Leu159Leu	synonymous_variant	Exon 5 of 26	ENST00000354181.8	NP_001352017.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC12A6	ENST00000354181.8 link	c.475C>T	p.Leu159Leu	synonymous_variant	Exon 5 of 26	1	NM_001365088.1	ENSP00000346112.3		Q9UHW9-1

Frequencies

GnomAD3 genomes

AF:

0.234

AC:

35590

AN:

151948

Hom.:

4245

Cov.:

show subpopulations

Gnomad AFR

AF:

0.216

Gnomad AMI

AF:

0.362

Gnomad AMR

AF:

0.192

Gnomad ASJ

AF:

0.253

Gnomad EAS

AF:

0.344

Gnomad SAS

AF:

0.347

Gnomad FIN

AF:

0.190

Gnomad MID

AF:

0.316

Gnomad NFE

AF:

0.243

Gnomad OTH

AF:

0.220

GnomAD2 exomes

AF:

0.247

AC:

62185

AN:

251478

AF XY:

0.253

show subpopulations

Gnomad AFR exome

AF:

0.218

Gnomad AMR exome

AF:

0.183

Gnomad ASJ exome

AF:

0.251

Gnomad EAS exome

AF:

0.340

Gnomad FIN exome

AF:

0.182

Gnomad NFE exome

AF:

0.243

Gnomad OTH exome

AF:

0.246

GnomAD4 exome

AF:

0.245

AC:

357005

AN:

1459670

Hom.:

44607

Cov.:

AF XY:

0.248

AC XY:

179973

AN XY:

726312

show subpopulations

African (AFR)

AF:

0.225

AC:

7509

AN:

33440

American (AMR)

AF:

0.185

AC:

8282

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.250

AC:

6534

AN:

26126

East Asian (EAS)

AF:

0.311

AC:

12355

AN:

39688

South Asian (SAS)

AF:

0.340

AC:

29290

AN:

86206

European-Finnish (FIN)

AF:

0.184

AC:

9838

AN:

53416

Middle Eastern (MID)

AF:

0.338

AC:

1948

AN:

5764

European-Non Finnish (NFE)

AF:

0.240

AC:

266134

AN:

1110000

Other (OTH)

AF:

0.251

AC:

15115

AN:

60316

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

12846

25692

38539

51385

64231

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.234

AC:

35612

AN:

152066

Hom.:

4240

Cov.:

AF XY:

0.235

AC XY:

17465

AN XY:

74314

show subpopulations

African (AFR)

AF:

0.217

AC:

8985

AN:

41476

American (AMR)

AF:

0.192

AC:

2927

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.253

AC:

878

AN:

3466

East Asian (EAS)

AF:

0.343

AC:

1775

AN:

5168

South Asian (SAS)

AF:

0.347

AC:

1666

AN:

4804

European-Finnish (FIN)

AF:

0.190

AC:

2005

AN:

10560

Middle Eastern (MID)

AF:

0.313

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.242

AC:

16490

AN:

68002

Other (OTH)

AF:

0.221

AC:

465

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1430

2860

4291

5721

7151

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.247

Hom.:

4200

Bravo

AF:

0.232

Asia WGS

AF:

0.294

AC:

1022

AN:

3478

EpiCase

AF:

0.249

EpiControl

AF:

0.245

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

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

- -

Feb 08, 2013

Genetic Services Laboratory, University of Chicago

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Agenesis of the corpus callosum with peripheral neuropathy

Benign:4

Jul 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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. -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Nov 21, 2019

Natera, Inc.

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:3

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

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.45

CADD

Benign

8.1

(source)

DANN

Benign

0.82

PhyloP100

1.7

Mutation Taster

=99/1

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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rs7164902

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