15-34250671-C-G

Position:

chr15-34250671-C-G

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The ENST00000354181.8(SLC12A6):c.1551G>C(p.Pro517=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.177 in 1,599,874 control chromosomes in the GnomAD database, including 25,941 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. P517P) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.17 ( 2188 hom., cov: 32)

Exomes 𝑓: 0.18 ( 23753 hom. )

Consequence

SLC12A6
ENST00000354181.8 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.174

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.43).

BP6

Variant 15-34250671-C-G is Benign according to our data. Variant chr15-34250671-C-G is described in ClinVar as [Benign]. Clinvar id is 139121.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-34250671-C-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.174 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.274 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC12A6	NM_001365088.1 linkuse as main transcript	c.1551G>C	p.Pro517=	synonymous_variant	12/26	ENST00000354181.8	NP_001352017.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC12A6	ENST00000354181.8 linkuse as main transcript	c.1551G>C	p.Pro517=	synonymous_variant	12/26	1	NM_001365088.1	ENSP00000346112	A1	Q9UHW9-1

Frequencies

GnomAD3 genomes

AF:

0.167

AC:

25369

AN:

151982

Hom.:

2193

Cov.:

show subpopulations

Gnomad AFR

AF:

0.129

Gnomad AMI

AF:

0.177

Gnomad AMR

AF:

0.178

Gnomad ASJ

AF:

0.191

Gnomad EAS

AF:

0.286

Gnomad SAS

AF:

0.226

Gnomad FIN

AF:

0.158

Gnomad MID

AF:

0.268

Gnomad NFE

AF:

0.173

Gnomad OTH

AF:

0.181

GnomAD3 exomes

AF:

0.189

AC:

47439

AN:

251268

Hom.:

4667

AF XY:

0.191

AC XY:

25889

AN XY:

135814

show subpopulations

Gnomad AFR exome

AF:

0.126

Gnomad AMR exome

AF:

0.190

Gnomad ASJ exome

AF:

0.184

Gnomad EAS exome

AF:

0.282

Gnomad SAS exome

AF:

0.227

Gnomad FIN exome

AF:

0.166

Gnomad NFE exome

AF:

0.177

Gnomad OTH exome

AF:

0.196

GnomAD4 exome

AF:

0.178

AC:

257555

AN:

1447774

Hom.:

23753

Cov.:

AF XY:

0.180

AC XY:

129571

AN XY:

721100

show subpopulations

Gnomad4 AFR exome

AF:

0.129

Gnomad4 AMR exome

AF:

0.189

Gnomad4 ASJ exome

AF:

0.188

Gnomad4 EAS exome

AF:

0.251

Gnomad4 SAS exome

AF:

0.225

Gnomad4 FIN exome

AF:

0.173

Gnomad4 NFE exome

AF:

0.172

Gnomad4 OTH exome

AF:

0.185

GnomAD4 genome

AF:

0.167

AC:

25370

AN:

152100

Hom.:

2188

Cov.:

AF XY:

0.169

AC XY:

12591

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.129

Gnomad4 AMR

AF:

0.178

Gnomad4 ASJ

AF:

0.191

Gnomad4 EAS

AF:

0.286

Gnomad4 SAS

AF:

0.227

Gnomad4 FIN

AF:

0.158

Gnomad4 NFE

AF:

0.173

Gnomad4 OTH

AF:

0.180

Alfa

AF:

0.117

Hom.:

253

Bravo

AF:

0.166

Asia WGS

AF:

0.229

AC:

796

AN:

3478

EpiCase

AF:

0.182

EpiControl

AF:

0.185

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Feb 08, 2013	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 28, 2014	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. -
Benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Dec 14, 2020	- -

Agenesis of the corpus callosum with peripheral neuropathy

Benign:4

Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 10, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	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. -
Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Sep 16, 2020	- -

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Benign

0.71

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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