15-34230841-C-CAG

Variant summary

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

The NM_001365088.1(SLC12A6):c.*3039_*3040insCT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0555 in 152,668 control chromosomes in the GnomAD database, including 288 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.055 (288 hom., cov: 31)
  • Exomes 𝑓: 0.080 (0 hom.)
• Consequence: SLC12A6 NM_001365088.1 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.23

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 15-34230841-C-CAG is Benign according to our data. Variant chr15-34230841-C-CAG is described in ClinVar as [Likely_benign]. Clinvar id is 315557.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.071 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC12A6	NM_001365088.1	c.*3039_*3040insCT		3_prime_UTR_variant	26/26	ENST00000354181.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC12A6	ENST00000354181.8	c.*3039_*3040insCT		3_prime_UTR_variant	26/26	1	NM_001365088.1	A1
SLC12A6	ENST00000290209.9	c.*3039_*3040insCT		3_prime_UTR_variant	25/25	1		P3
SLC12A6	ENST00000676379.1	c.*1658_*1659insCT		3_prime_UTR_variant	26/26

Frequencies

GnomAD3 genomes AF: 0.0555 AC: 8445 AN: 152110 Hom.: 288 Cov.: 31

Gnomad AFR AF: 0.0238

Gnomad AMI AF: 0.0625

Gnomad AMR AF: 0.0517

Gnomad ASJ AF: 0.0784

Gnomad EAS AF: 0.00922

Gnomad SAS AF: 0.0462

Gnomad FIN AF: 0.0936

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0727

Gnomad OTH AF: 0.0540

GnomAD4 exome AF: 0.0795 AC: 35 AN: 440 Hom.: 0 Cov.: 0 AF XY: 0.0878 AC XY: 23 AN XY: 262

Gnomad4 FIN exome AF: 0.0822

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0554 AC: 8441 AN: 152228 Hom.: 288 Cov.: 31 AF XY: 0.0555 AC XY: 4133 AN XY: 74422

Gnomad4 AFR AF: 0.0237

Gnomad4 AMR AF: 0.0516

Gnomad4 ASJ AF: 0.0784

Gnomad4 EAS AF: 0.00924

Gnomad4 SAS AF: 0.0462

Gnomad4 FIN AF: 0.0936

Gnomad4 NFE AF: 0.0727

Gnomad4 OTH AF: 0.0535

Alfa AF: 0.0592 Hom.: 11

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

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Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs145421659; hg19: chr15-34523042; COSMIC: COSV50785029; COSMIC: COSV50785029;