Variant rs3746519 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.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

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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/exons	MANE	Protein	UniProt
SLC12A5	NM_020708.5 linkuse as main transcript	c.534T>C	p.Gly178Gly	synonymous_variant	6/26	ENST00000243964.7	NP_065759.1	Q9H2X9-2
SLC12A5	NM_001134771.2 linkuse as main transcript	c.603T>C	p.Gly201Gly	synonymous_variant	6/26		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.534T>C	p.Gly178Gly	synonymous_variant	6/26	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

GnomAD3 exomes

AF:

0.0411

AC:

10297

AN:

250386

Hom.:

527

AF XY:

0.0370

AC XY:

5014

AN XY:

135374

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 SAS exome

AF:

0.0300

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

Gnomad4 AFR exome

AF:

0.00511

Gnomad4 AMR exome

AF:

0.149

Gnomad4 ASJ exome

AF:

0.0529

Gnomad4 EAS exome

AF:

0.0346

Gnomad4 SAS exome

AF:

0.0298

Gnomad4 FIN exome

AF:

0.0192

Gnomad4 NFE exome

AF:

0.0225

Gnomad4 OTH exome

AF:

0.0296

GnomAD4 genome

AF:

0.0291

AC:

4417

AN:

151972

Hom.:

170

Cov.:

AF XY:

0.0309

AC XY:

2297

AN XY:

74258

show subpopulations

Gnomad4 AFR

AF:

0.00801

Gnomad4 AMR

AF:

0.118

Gnomad4 ASJ

AF:

0.0539

Gnomad4 EAS

AF:

0.0275

Gnomad4 SAS

AF:

0.0273

Gnomad4 FIN

AF:

0.0184

Gnomad4 NFE

AF:

0.0223

Gnomad4 OTH

AF:

0.0350

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

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

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

-0.54

CADD

Benign

7.3

DANN

Benign

0.74

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