rs3746519

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_020708.5(SLC12A5):c.534T>C(p.Gly178Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0276 in 1,612,408 control chromosomes in the GnomAD database, including 1,188 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.029 ( 170 hom., cov: 31)

Exomes 𝑓: 0.027 ( 1018 hom. )

Consequence

SLC12A5
NM_020708.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.419

Publications

7 publications found

Variant links:

Genes affected

SLC12A5 (HGNC:13818): (solute carrier family 12 member 5) K-Cl cotransporters are proteins that lower intracellular chloride concentrations below the electrochemical equilibrium potential. The protein encoded by this gene is an integral membrane K-Cl cotransporter that can function in either a net efflux or influx pathway, depending on the chemical concentration gradients of potassium and chloride. The encoded protein can act as a homomultimer, or as a heteromultimer with other K-Cl cotransporters, to maintain chloride homeostasis in neurons. Alternative splicing results in two transcript variants encoding different isoforms. [provided by RefSeq, Sep 2008]

SLC12A5 Gene-Disease associations (from GenCC):

developmental and epileptic encephalopathy, 34
Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Illumina, Ambry Genetics
epilepsy of infancy with migrating focal seizures
Inheritance: AR Classification: STRONG Submitted by: G2P
malignant migrating partial seizures of infancy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
epilepsy, idiopathic generalized, susceptibility to, 14
Inheritance: AD Classification: LIMITED, NO_KNOWN Submitted by: Illumina, Ambry Genetics
genetic developmental and epileptic encephalopathy
Inheritance: AR Classification: LIMITED Submitted by: ClinGen

SLC12A5 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP6

Variant 20-46037307-T-C is Benign according to our data. Variant chr20-46037307-T-C is described in ClinVar as Benign. ClinVar VariationId is 475658.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.419 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.114 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC12A5	NM_020708.5 link	c.534T>C	p.Gly178Gly	synonymous_variant	Exon 6 of 26	ENST00000243964.7	NP_065759.1	Q9H2X9-2
SLC12A5	NM_001134771.2 link	c.603T>C	p.Gly201Gly	synonymous_variant	Exon 6 of 26		NP_001128243.1	Q9H2X9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC12A5	ENST00000243964.7 link	c.534T>C	p.Gly178Gly	synonymous_variant	Exon 6 of 26	1	NM_020708.5	ENSP00000243964.4		Q9H2X9-2

Frequencies

GnomAD3 genomes

AF:

0.0291

AC:

4412

AN:

151854

Hom.:

167

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00804

Gnomad AMI

AF:

0.0395

Gnomad AMR

AF:

0.118

Gnomad ASJ

AF:

0.0539

Gnomad EAS

AF:

0.0276

Gnomad SAS

AF:

0.0273

Gnomad FIN

AF:

0.0184

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0223

Gnomad OTH

AF:

0.0344

GnomAD2 exomes

AF:

0.0411

AC:

10297

AN:

250386

AF XY:

0.0370

show subpopulations

Gnomad AFR exome

AF:

0.00567

Gnomad AMR exome

AF:

0.150

Gnomad ASJ exome

AF:

0.0513

Gnomad EAS exome

AF:

0.0289

Gnomad FIN exome

AF:

0.0215

Gnomad NFE exome

AF:

0.0212

Gnomad OTH exome

AF:

0.0387

GnomAD4 exome

AF:

0.0274

AC:

40065

AN:

1460436

Hom.:

1018

Cov.:

AF XY:

0.0271

AC XY:

19710

AN XY:

726598

show subpopulations

African (AFR)

AF:

0.00511

AC:

171

AN:

33446

American (AMR)

AF:

0.149

AC:

6654

AN:

44522

Ashkenazi Jewish (ASJ)

AF:

0.0529

AC:

1379

AN:

26058

East Asian (EAS)

AF:

0.0346

AC:

1370

AN:

39632

South Asian (SAS)

AF:

0.0298

AC:

2569

AN:

86162

European-Finnish (FIN)

AF:

0.0192

AC:

1026

AN:

53398

Middle Eastern (MID)

AF:

0.0146

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

0.0225

AC:

25024

AN:

1111132

Other (OTH)

AF:

0.0296

AC:

1788

AN:

60330

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

1995

3990

5984

7979

9974

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1058

2116

3174

4232

5290

<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:

0.0291

AC:

4417

AN:

151972

Hom.:

170

Cov.:

AF XY:

0.0309

AC XY:

2297

AN XY:

74258

show subpopulations

African (AFR)

AF:

0.00801

AC:

332

AN:

41434

American (AMR)

AF:

0.118

AC:

1803

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.0539

AC:

187

AN:

3470

East Asian (EAS)

AF:

0.0275

AC:

142

AN:

5162

South Asian (SAS)

AF:

0.0273

AC:

131

AN:

4800

European-Finnish (FIN)

AF:

0.0184

AC:

194

AN:

10560

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0223

AC:

1516

AN:

67960

Other (OTH)

AF:

0.0350

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

219

438

656

875

1094

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

156

208

260

<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:

0.0231

Hom.:

Bravo

AF:

0.0348

Asia WGS

AF:

0.0270

AC:

AN:

3478

EpiCase

AF:

0.0229

EpiControl

AF:

0.0244

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Nov 12, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Developmental and epileptic encephalopathy, 34

Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

-0.54

CADD

Benign

7.3

(source)

DANN

Benign

0.74

PhyloP100

-0.42

Mutation Taster

=89/11

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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