15-34230734-GAGAC-G

Position:

• chr15-34230734-GAGAC-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001365088.1(SLC12A6):​c.*3143_*3146del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.171 in 152,498 control chromosomes in the GnomAD database, including 2,281 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.17 (2277 hom., cov: 28)
  • Exomes 𝑓: 0.14 (4 hom.)
• Consequence: SLC12A6 NM_001365088.1 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.32

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 -10 ACMG points.

• BP6: Variant 15-34230734-GAGAC-G is Benign according to our data. Variant chr15-34230734-GAGAC-G is described in ClinVar as [Likely_benign]. Clinvar id is 315555.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.267 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC12A6	NM_001365088.1	c.*3143_*3146del		3_prime_UTR_variant	26/26	ENST00000354181.8	NP_001352017.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC12A6	ENST00000354181.8	c.*3143_*3146del		3_prime_UTR_variant	26/26	1	NM_001365088.1	ENSP00000346112	A1
SLC12A6	ENST00000290209.9	c.*3143_*3146del		3_prime_UTR_variant	25/25	1		ENSP00000290209	P3
SLC12A6	ENST00000676379.1	c.*1762_*1765del		3_prime_UTR_variant	26/26			ENSP00000502539

Frequencies

GnomAD3 genomes AF: 0.172 AC: 26066 AN: 151940 Hom.: 2282 Cov.: 28

Gnomad AFR AF: 0.143

Gnomad AMI AF: 0.175

Gnomad AMR AF: 0.179

Gnomad ASJ AF: 0.192

Gnomad EAS AF: 0.279

Gnomad SAS AF: 0.227

Gnomad FIN AF: 0.157

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.175

Gnomad OTH AF: 0.188

GnomAD4 exome AF: 0.141 AC: 62 AN: 440 Hom.: 4 AF XY: 0.138 AC XY: 37 AN XY: 268

Gnomad4 FIN exome AF: 0.143

Gnomad4 NFE exome AF: 0.125

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.171 AC: 26065 AN: 152058 Hom.: 2277 Cov.: 28 AF XY: 0.173 AC XY: 12870 AN XY: 74312

Gnomad4 AFR AF: 0.142

Gnomad4 AMR AF: 0.180

Gnomad4 ASJ AF: 0.192

Gnomad4 EAS AF: 0.279

Gnomad4 SAS AF: 0.228

Gnomad4 FIN AF: 0.157

Gnomad4 NFE AF: 0.175

Gnomad4 OTH AF: 0.188

Alfa AF: 0.168 Hom.: 251

Bravo AF: 0.172

Asia WGS AF: 0.228 AC: 794 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Agenesis of the corpus callosum with peripheral neuropathy Benign:1

Likely benign, 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: rs143386876; hg19: chr15-34522935;