Variant 20-46023148-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001134771.2(SLC12A5):c.121+1262C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0292 in 398,070 control chromosomes in the GnomAD database, including 345 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.029 ( 174 hom., cov: 32)

Exomes 𝑓: 0.029 ( 171 hom. )

Consequence

SLC12A5
NM_001134771.2 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.199

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 20-46023148-C-T is Benign according to our data. Variant chr20-46023148-C-T is described in ClinVar as [Benign]. Clinvar id is 3255309.Status of the report is criteria_provided_single_submitter, 1 stars.

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_001134771.2 linkuse as main transcript	c.121+1262C>T		intron_variant			NP_001128243.1	Q9H2X9-1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	Protein	UniProt
SLC12A5	ENST00000454036.6 linkuse as main transcript	c.121+1262C>T	intron_variant	5	ENSP00000387694.1	Q9H2X9-1
SLC12A5	ENST00000626701.1 linkuse as main transcript	c.350+77C>T	intron_variant	3	ENSP00000487372.1	A0A0D9SGD0
SLC12A5	ENST00000413737.2 linkuse as main transcript	c.188+77C>T	intron_variant	3	ENSP00000487291.1	A0A0D9SGA5

Frequencies

GnomAD3 genomes

AF:

0.0290

AC:

4411

AN:

152086

Hom.:

171

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00780

Gnomad AMI

AF:

0.0844

Gnomad AMR

AF:

0.119

Gnomad ASJ

AF:

0.0533

Gnomad EAS

AF:

0.0299

Gnomad SAS

AF:

0.0243

Gnomad FIN

AF:

0.0183

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0218

Gnomad OTH

AF:

0.0330

GnomAD4 exome

AF:

0.0294

AC:

7218

AN:

245866

Hom.:

171

Cov.:

AF XY:

0.0291

AC XY:

3631

AN XY:

124580

show subpopulations

Gnomad4 AFR exome

AF:

0.00766

Gnomad4 AMR exome

AF:

0.144

Gnomad4 ASJ exome

AF:

0.0522

Gnomad4 EAS exome

AF:

0.0475

Gnomad4 SAS exome

AF:

0.0318

Gnomad4 FIN exome

AF:

0.0178

Gnomad4 NFE exome

AF:

0.0218

Gnomad4 OTH exome

AF:

0.0363

GnomAD4 genome

AF:

0.0290

AC:

4417

AN:

152204

Hom.:

174

Cov.:

AF XY:

0.0310

AC XY:

2310

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.00777

Gnomad4 AMR

AF:

0.119

Gnomad4 ASJ

AF:

0.0533

Gnomad4 EAS

AF:

0.0298

Gnomad4 SAS

AF:

0.0247

Gnomad4 FIN

AF:

0.0183

Gnomad4 NFE

AF:

0.0217

Gnomad4 OTH

AF:

0.0331

Alfa

AF:

0.0231

Hom.:

Bravo

AF:

0.0354

Asia WGS

AF:

0.0290

AC:

100

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

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 24% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 22. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

8.3

DANN

Benign

0.86

Splicing

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