20-46023148-C-T

Variant names:

• chr20-46023148-C-T
• rs12479993
• NM_001134771.2:c.121+1262C>T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.199

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]

ACMG classification

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 rank	MANE	Protein	UniProt
SLC12A5	NM_001134771.2	c.121+1262C>T		intron_variant	Intron 1 of 25		NP_001128243.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC12A5	ENST00000454036.6	c.121+1262C>T		intron_variant	Intron 1 of 25	5		ENSP00000387694.1
SLC12A5	ENST00000626701.1	c.350+77C>T		intron_variant	Intron 2 of 2	3		ENSP00000487372.1
SLC12A5	ENST00000413737.2	c.188+77C>T		intron_variant	Intron 2 of 2	3		ENSP00000487291.1

Frequencies

GnomAD3 genomes AF: 0.0290 AC: 4411 AN: 152086 Hom.: 171 Cov.: 32

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.: 0 AF XY: 0.0291 AC XY: 3631 AN XY: 124580

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.: 32 AF XY: 0.0310 AC XY: 2310 AN XY: 74420

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.: 11

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

Submissions by phenotype

not specified Benign:1

Jul 15, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

Other links and lift over

dbSNP: rs12479993; hg19: chr20-44651787;