rs426634

Positions:

• chr15-34279723-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000354181.8(SLC12A6):​c.272-4334G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.385 in 152,112 control chromosomes in the GnomAD database, including 14,300 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.38 (14300 hom., cov: 32)
• Consequence: SLC12A6 ENST00000354181.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.203

Genes affected

SLC12A6 (HGNC:10914): (solute carrier family 12 member 6) This gene is a member of the K-Cl cotransporter (KCC) family. K-Cl cotransporters are integral membrane proteins that lower intracellular chloride concentrations below the electrochemical equilibrium potential. The proteins encoded by this gene are activated by cell swelling induced by hypotonic conditions. Alternate splicing results in multiple transcript variants encoding different isoforms. Mutations in this gene are associated with agenesis of the corpus callosum with peripheral neuropathy. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.699 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC12A6	NM_001365088.1	c.272-4334G>A		intron_variant		ENST00000354181.8	NP_001352017.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC12A6	ENST00000354181.8	c.272-4334G>A		intron_variant		1	NM_001365088.1	ENSP00000346112	A1

Frequencies

GnomAD3 genomes AF: 0.384 AC: 58411 AN: 151994 Hom.: 14270 Cov.: 32

Gnomad AFR AF: 0.706

Gnomad AMI AF: 0.395

Gnomad AMR AF: 0.254

Gnomad ASJ AF: 0.289

Gnomad EAS AF: 0.322

Gnomad SAS AF: 0.363

Gnomad FIN AF: 0.202

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.259

Gnomad OTH AF: 0.329

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.385 AC: 58499 AN: 152112 Hom.: 14300 Cov.: 32 AF XY: 0.379 AC XY: 28208 AN XY: 74356

Gnomad4 AFR AF: 0.706

Gnomad4 AMR AF: 0.253

Gnomad4 ASJ AF: 0.289

Gnomad4 EAS AF: 0.322

Gnomad4 SAS AF: 0.362

Gnomad4 FIN AF: 0.202

Gnomad4 NFE AF: 0.259

Gnomad4 OTH AF: 0.328

Alfa AF: 0.299 Hom.: 3663

Bravo AF: 0.401

Asia WGS AF: 0.329 AC: 1146 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.8
DANN	Benign	0.15

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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

Other links and lift over

dbSNP: rs426634; hg19: chr15-34571924;