Variant rs3848724 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_020708.5(SLC12A5):c.355C>A(p.Arg119=) 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 1,614,082 control chromosomes in the GnomAD database, including 1,189 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. R119R) has been classified as Benign.

Frequency

Genomes: 𝑓 0.029 ( 173 hom., cov: 32)

Exomes 𝑓: 0.027 ( 1016 hom. )

Consequence

SLC12A5
NM_020708.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.61

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:

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=-0.24).

BP6

Variant 20-46035852-C-A is Benign according to our data. Variant chr20-46035852-C-A is described in ClinVar as [Benign]. Clinvar id is 475656.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.61 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/exons	MANE	UniProt
SLC12A5	NM_020708.5 linkuse as main transcript	c.355C>A	p.Arg119=	synonymous_variant	4/26	ENST00000243964.7
SLC12A5	NM_001134771.2 linkuse as main transcript	c.424C>A	p.Arg142=	synonymous_variant	4/26

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC12A5	ENST00000243964.7 linkuse as main transcript	c.355C>A	p.Arg119=	synonymous_variant	4/26	1	NM_020708.5	A1	Q9H2X9-2

Frequencies

GnomAD3 genomes

AF:

0.0291

AC:

4428

AN:

152238

Hom.:

170

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00799

Gnomad AMI

AF:

0.0395

Gnomad AMR

AF:

0.118

Gnomad ASJ

AF:

0.0539

Gnomad EAS

AF:

0.0283

Gnomad SAS

AF:

0.0273

Gnomad FIN

AF:

0.0184

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0224

Gnomad OTH

AF:

0.0340

GnomAD3 exomes

AF:

0.0414

AC:

10390

AN:

251198

Hom.:

531

AF XY:

0.0373

AC XY:

5065

AN XY:

135806

show subpopulations

Gnomad AFR exome

AF:

0.00572

Gnomad AMR exome

AF:

0.150

Gnomad ASJ exome

AF:

0.0513

Gnomad EAS exome

AF:

0.0293

Gnomad SAS exome

AF:

0.0302

Gnomad FIN exome

AF:

0.0218

Gnomad NFE exome

AF:

0.0214

Gnomad OTH exome

AF:

0.0390

GnomAD4 exome

AF:

0.0275

AC:

40179

AN:

1461728

Hom.:

1016

Cov.:

AF XY:

0.0272

AC XY:

19774

AN XY:

727182

show subpopulations

Gnomad4 AFR exome

AF:

0.00517

Gnomad4 AMR exome

AF:

0.150

Gnomad4 ASJ exome

AF:

0.0529

Gnomad4 EAS exome

AF:

0.0354

Gnomad4 SAS exome

AF:

0.0299

Gnomad4 FIN exome

AF:

0.0193

Gnomad4 NFE exome

AF:

0.0225

Gnomad4 OTH exome

AF:

0.0298

GnomAD4 genome

AF:

0.0291

AC:

4433

AN:

152354

Hom.:

173

Cov.:

AF XY:

0.0309

AC XY:

2301

AN XY:

74510

show subpopulations

Gnomad4 AFR

AF:

0.00796

Gnomad4 AMR

AF:

0.118

Gnomad4 ASJ

AF:

0.0539

Gnomad4 EAS

AF:

0.0281

Gnomad4 SAS

AF:

0.0273

Gnomad4 FIN

AF:

0.0184

Gnomad4 NFE

AF:

0.0223

Gnomad4 OTH

AF:

0.0346

Alfa

AF:

0.0233

Hom.:

Bravo

AF:

0.0349

Asia WGS

AF:

0.0270

AC:

AN:

3478

EpiCase

AF:

0.0231

EpiControl

AF:

0.0244

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

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

Invitae

Feb 01, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.24

CADD

Benign

9.7

DANN

Benign

0.65

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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