20-46043241-C-T

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.1155C>T(p.Ile385Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0277 in 1,613,964 control chromosomes in the GnomAD database, including 1,179 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: 0.028 ( 1009 hom. )

Consequence

SLC12A5
NM_020708.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -2.19

Publications

8 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=-0.55).

BP6

Variant 20-46043241-C-T is Benign according to our data. Variant chr20-46043241-C-T is described in ClinVar as Benign. ClinVar VariationId is 475640.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.19 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.113 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC12A5	NM_020708.5 link	c.1155C>T	p.Ile385Ile	synonymous_variant	Exon 9 of 26	ENST00000243964.7	NP_065759.1	Q9H2X9-2
SLC12A5	NM_001134771.2 link	c.1224C>T	p.Ile408Ile	synonymous_variant	Exon 9 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.1155C>T	p.Ile385Ile	synonymous_variant	Exon 9 of 26	1	NM_020708.5	ENSP00000243964.4		Q9H2X9-2

Frequencies

GnomAD3 genomes

AF:

0.0290

AC:

4405

AN:

151982

Hom.:

167

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00800

Gnomad AMI

AF:

0.0395

Gnomad AMR

AF:

0.117

Gnomad ASJ

AF:

0.0539

Gnomad EAS

AF:

0.0276

Gnomad SAS

AF:

0.0271

Gnomad FIN

AF:

0.0183

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0225

Gnomad OTH

AF:

0.0336

GnomAD2 exomes

AF:

0.0413

AC:

10375

AN:

251420

AF XY:

0.0372

show subpopulations

Gnomad AFR exome

AF:

0.00572

Gnomad AMR exome

AF:

0.149

Gnomad ASJ exome

AF:

0.0511

Gnomad EAS exome

AF:

0.0292

Gnomad FIN exome

AF:

0.0217

Gnomad NFE exome

AF:

0.0215

Gnomad OTH exome

AF:

0.0393

GnomAD4 exome

AF:

0.0276

AC:

40291

AN:

1461864

Hom.:

1009

Cov.:

AF XY:

0.0273

AC XY:

19824

AN XY:

727238

show subpopulations

African (AFR)

AF:

0.00511

AC:

171

AN:

33480

American (AMR)

AF:

0.149

AC:

6641

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.0528

AC:

1381

AN:

26136

East Asian (EAS)

AF:

0.0347

AC:

1377

AN:

39700

South Asian (SAS)

AF:

0.0300

AC:

2590

AN:

86258

European-Finnish (FIN)

AF:

0.0194

AC:

1034

AN:

53420

Middle Eastern (MID)

AF:

0.0154

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0227

AC:

25208

AN:

1111988

Other (OTH)

AF:

0.0298

AC:

1800

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

2118

4237

6355

8474

10592

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1064

2128

3192

4256

5320

<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:

0.0290

AC:

4410

AN:

152100

Hom.:

170

Cov.:

AF XY:

0.0309

AC XY:

2294

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.00798

AC:

331

AN:

41504

American (AMR)

AF:

0.117

AC:

1789

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.0539

AC:

187

AN:

3470

East Asian (EAS)

AF:

0.0275

AC:

142

AN:

5166

South Asian (SAS)

AF:

0.0271

AC:

130

AN:

4800

European-Finnish (FIN)

AF:

0.0183

AC:

194

AN:

10600

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0225

AC:

1527

AN:

67982

Other (OTH)

AF:

0.0342

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

202

404

606

808

1010

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:

0.0245

Hom.:

Bravo

AF:

0.0347

Asia WGS

AF:

0.0270

AC:

AN:

3478

EpiCase

AF:

0.0233

EpiControl

AF:

0.0247

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Nov 12, 2018

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

- -

not specified

Benign:1

Jul 15, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 23% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 21. Only high quality variants are reported. -

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

-0.55

CADD

Benign

2.3

(source)

DANN

Benign

0.52

PhyloP100

-2.2

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.14

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