15-34230971-GA-G

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BS1_Supporting

The NM_001365088.1(SLC12A6):c.*2909del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00161 in 150,094 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0016 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SLC12A6 NM_001365088.1 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.513

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 Likely_benign. Variant got -1 ACMG points.

• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00161 (241/150094) while in subpopulation SAS AF= 0.00358 (17/4752). AF 95% confidence interval is 0.00228. There are 1 homozygotes in gnomad4. There are 125 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC12A6	NM_001365088.1	c.*2909del		3_prime_UTR_variant	26/26	ENST00000354181.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC12A6	ENST00000354181.8	c.*2909del		3_prime_UTR_variant	26/26	1	NM_001365088.1	A1
SLC12A6	ENST00000290209.9	c.*2909del		3_prime_UTR_variant	25/25	1		P3
SLC12A6	ENST00000676379.1	c.*1528del		3_prime_UTR_variant	26/26

Frequencies

GnomAD3 genomes AF: 0.00161 AC: 241 AN: 149988 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00222

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00120

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000389

Gnomad SAS AF: 0.00357

Gnomad FIN AF: 0.000100

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00157

Gnomad OTH AF: 0.00291

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 10 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 8

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.00161 AC: 241 AN: 150094 Hom.: 1 Cov.: 32 AF XY: 0.00171 AC XY: 125 AN XY: 73188

Gnomad4 AFR AF: 0.00222

Gnomad4 AMR AF: 0.00119

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000390

Gnomad4 SAS AF: 0.00358

Gnomad4 FIN AF: 0.000100

Gnomad4 NFE AF: 0.00157

Gnomad4 OTH AF: 0.00288

Bravo AF: 0.00169

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Agenesis of the corpus callosum with peripheral neuropathy Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

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: rs886051039; hg19: chr15-34523172;