Variant 20-46048088-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_020708.5(SLC12A5):c.2012+3T>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0275 in 1,608,780 control chromosomes in the GnomAD database, including 1,049 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.030 ( 164 hom., cov: 31)

Exomes 𝑓: 0.027 ( 885 hom. )

Consequence

SLC12A5
NM_020708.5 splice_region, intron

Scores

Splicing: ADA: 0.00005421

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.946

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BP6

Variant 20-46048088-T-A is Benign according to our data. Variant chr20-46048088-T-A is described in ClinVar as [Benign]. Clinvar id is 475644.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.107 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC12A5	NM_020708.5 link	c.2012+3T>A		splice_region_variant, intron_variant		ENST00000243964.7	NP_065759.1	Q9H2X9-2
SLC12A5	NM_001134771.2 link	c.2081+3T>A		splice_region_variant, intron_variant			NP_001128243.1	Q9H2X9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC12A5	ENST00000243964.7 link	c.2012+3T>A		splice_region_variant, intron_variant		1	NM_020708.5	ENSP00000243964.4		Q9H2X9-2

Frequencies

GnomAD3 genomes

AF:

0.0303

AC:

4597

AN:

151894

Hom.:

162

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0143

Gnomad AMI

AF:

0.0406

Gnomad AMR

AF:

0.111

Gnomad ASJ

AF:

0.0530

Gnomad EAS

AF:

0.0249

Gnomad SAS

AF:

0.0263

Gnomad FIN

AF:

0.0190

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0230

Gnomad OTH

AF:

0.0364

GnomAD3 exomes

AF:

0.0396

AC:

9514

AN:

240124

Hom.:

392

AF XY:

0.0363

AC XY:

4706

AN XY:

129662

show subpopulations

Gnomad AFR exome

AF:

0.0128

Gnomad AMR exome

AF:

0.128

Gnomad ASJ exome

AF:

0.0497

Gnomad EAS exome

AF:

0.0341

Gnomad SAS exome

AF:

0.0309

Gnomad FIN exome

AF:

0.0224

Gnomad NFE exome

AF:

0.0219

Gnomad OTH exome

AF:

0.0378

GnomAD4 exome

AF:

0.0272

AC:

39618

AN:

1456768

Hom.:

885

Cov.:

AF XY:

0.0270

AC XY:

19522

AN XY:

724060

show subpopulations

Gnomad4 AFR exome

AF:

0.0125

Gnomad4 AMR exome

AF:

0.128

Gnomad4 ASJ exome

AF:

0.0517

Gnomad4 EAS exome

AF:

0.0231

Gnomad4 SAS exome

AF:

0.0299

Gnomad4 FIN exome

AF:

0.0197

Gnomad4 NFE exome

AF:

0.0233

Gnomad4 OTH exome

AF:

0.0308

GnomAD4 genome

AF:

0.0303

AC:

4606

AN:

152012

Hom.:

164

Cov.:

AF XY:

0.0320

AC XY:

2381

AN XY:

74328

show subpopulations

Gnomad4 AFR

AF:

0.0143

Gnomad4 AMR

AF:

0.111

Gnomad4 ASJ

AF:

0.0530

Gnomad4 EAS

AF:

0.0252

Gnomad4 SAS

AF:

0.0261

Gnomad4 FIN

AF:

0.0190

Gnomad4 NFE

AF:

0.0229

Gnomad4 OTH

AF:

0.0370

Alfa

AF:

0.0256

Hom.:

Bravo

AF:

0.0354

Asia WGS

AF:

0.0250

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Developmental and epileptic encephalopathy, 34

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 04, 2025

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

0.051

DANN

Benign

0.70

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000054

dbscSNV1_RF

Benign

0.070

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