dbSNP rs2290941: SLC12A6:c.1333+20G>T (chr15-34252150-C-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001365088.1(SLC12A6):c.1333+20G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.177 in 1,314,282 control chromosomes in the GnomAD database, including 21,063 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.17 ( 2170 hom., cov: 31)

Exomes 𝑓: 0.18 ( 18893 hom. )

Consequence

SLC12A6
NM_001365088.1 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.495

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 15-34252150-C-A is Benign according to our data. Variant chr15-34252150-C-A is described in ClinVar as [Benign]. Clinvar id is 139120.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-34252150-C-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.272 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC12A6	NM_001365088.1 link	c.1333+20G>T		intron_variant	Intron 10 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.1333+20G>T		intron_variant	Intron 10 of 25	1	NM_001365088.1	ENSP00000346112.3		Q9UHW9-1

Frequencies

GnomAD3 genomes

AF:

0.166

AC:

25222

AN:

151836

Hom.:

2174

Cov.:

show subpopulations

Gnomad AFR

AF:

0.128

Gnomad AMI

AF:

0.175

Gnomad AMR

AF:

0.177

Gnomad ASJ

AF:

0.190

Gnomad EAS

AF:

0.284

Gnomad SAS

AF:

0.225

Gnomad FIN

AF:

0.159

Gnomad MID

AF:

0.266

Gnomad NFE

AF:

0.173

Gnomad OTH

AF:

0.181

GnomAD3 exomes

AF:

0.187

AC:

45594

AN:

243860

Hom.:

4355

AF XY:

0.189

AC XY:

24905

AN XY:

131872

show subpopulations

Gnomad AFR exome

AF:

0.123

Gnomad AMR exome

AF:

0.187

Gnomad ASJ exome

AF:

0.183

Gnomad EAS exome

AF:

0.278

Gnomad SAS exome

AF:

0.225

Gnomad FIN exome

AF:

0.165

Gnomad NFE exome

AF:

0.175

Gnomad OTH exome

AF:

0.195

GnomAD4 exome

AF:

0.178

AC:

206889

AN:

1162328

Hom.:

18893

Cov.:

AF XY:

0.180

AC XY:

106540

AN XY:

592542

show subpopulations

Gnomad4 AFR exome

AF:

0.125

Gnomad4 AMR exome

AF:

0.188

Gnomad4 ASJ exome

AF:

0.189

Gnomad4 EAS exome

AF:

0.249

Gnomad4 SAS exome

AF:

0.224

Gnomad4 FIN exome

AF:

0.172

Gnomad4 NFE exome

AF:

0.171

Gnomad4 OTH exome

AF:

0.184

GnomAD4 genome

AF:

0.166

AC:

25223

AN:

151954

Hom.:

2170

Cov.:

AF XY:

0.168

AC XY:

12505

AN XY:

74258

show subpopulations

Gnomad4 AFR

AF:

0.127

Gnomad4 AMR

AF:

0.178

Gnomad4 ASJ

AF:

0.190

Gnomad4 EAS

AF:

0.284

Gnomad4 SAS

AF:

0.226

Gnomad4 FIN

AF:

0.159

Gnomad4 NFE

AF:

0.173

Gnomad4 OTH

AF:

0.180

Alfa

AF:

0.168

Hom.:

455

Bravo

AF:

0.165

Asia WGS

AF:

0.227

AC:

791

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Feb 28, 2014

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Dec 14, 2020

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

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Genetic Services Laboratory, University of Chicago

Significance: Likely 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

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Agenesis of the corpus callosum with peripheral neuropathy

Benign:1

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

-0.79

CADD

Benign

DANN

Benign

0.68

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over