Variant rs35804246 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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

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 links:

SLC12A5 (HGNC:):

SLC12A5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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/exons	MANE	Protein	UniProt
SLC12A5	NM_020708.5 linkuse as main transcript	c.1155C>T	p.Ile385Ile	synonymous_variant	9/26	ENST00000243964.7	NP_065759.1	Q9H2X9-2
SLC12A5	NM_001134771.2 linkuse as main transcript	c.1224C>T	p.Ile408Ile	synonymous_variant	9/26		NP_001128243.1	Q9H2X9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC12A5	ENST00000243964.7 linkuse as main transcript	c.1155C>T	p.Ile385Ile	synonymous_variant	9/26	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

GnomAD3 exomes

AF:

0.0413

AC:

10375

AN:

251420

Hom.:

526

AF XY:

0.0372

AC XY:

5061

AN XY:

135894

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 SAS exome

AF:

0.0304

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

Gnomad4 AFR exome

AF:

0.00511

Gnomad4 AMR exome

AF:

0.149

Gnomad4 ASJ exome

AF:

0.0528

Gnomad4 EAS exome

AF:

0.0347

Gnomad4 SAS exome

AF:

0.0300

Gnomad4 FIN exome

AF:

0.0194

Gnomad4 NFE exome

AF:

0.0227

Gnomad4 OTH exome

AF:

0.0298

GnomAD4 genome

AF:

0.0290

AC:

4410

AN:

152100

Hom.:

170

Cov.:

AF XY:

0.0309

AC XY:

2294

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.00798

Gnomad4 AMR

AF:

0.117

Gnomad4 ASJ

AF:

0.0539

Gnomad4 EAS

AF:

0.0275

Gnomad4 SAS

AF:

0.0271

Gnomad4 FIN

AF:

0.0183

Gnomad4 NFE

AF:

0.0225

Gnomad4 OTH

AF:

0.0342

Alfa

AF:

0.0234

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

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jul 15, 2024

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

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

-0.55

CADD

Benign

2.3

DANN

Benign

0.52

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

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