NM_001365088.1:c.1584_1585delCTinsG
Variant summary
Our verdict is Pathogenic. The variant received 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_001365088.1(SLC12A6):c.1584_1585delCTinsG(p.Phe529LeufsTer4) variant causes a frameshift, missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Consequence
SLC12A6
NM_001365088.1 frameshift, missense
NM_001365088.1 frameshift, missense
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.213
Publications
3 publications found
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]
SLC12A6 Gene-Disease associations (from GenCC):
- agenesis of the corpus callosum with peripheral neuropathyInheritance: AD, AR Classification: DEFINITIVE, STRONG, SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae), Orphanet
- Charcot-Marie-Tooth disease, axonal, IIa 2IIInheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
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ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 11 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 15-34250637-AG-C is Pathogenic according to our data. Variant chr15-34250637-AG-C is described in CliVar as Pathogenic. Clinvar id is 136175.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr15-34250637-AG-C is described in CliVar as Pathogenic. Clinvar id is 136175.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr15-34250637-AG-C is described in CliVar as Pathogenic. Clinvar id is 136175.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr15-34250637-AG-C is described in CliVar as Pathogenic. Clinvar id is 136175.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr15-34250637-AG-C is described in CliVar as Pathogenic. Clinvar id is 136175.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr15-34250637-AG-C is described in CliVar as Pathogenic. Clinvar id is 136175.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr15-34250637-AG-C is described in CliVar as Pathogenic. Clinvar id is 136175.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr15-34250637-AG-C is described in CliVar as Pathogenic. Clinvar id is 136175.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr15-34250637-AG-C is described in CliVar as Pathogenic. Clinvar id is 136175.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr15-34250637-AG-C is described in CliVar as Pathogenic. Clinvar id is 136175.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr15-34250637-AG-C is described in CliVar as Pathogenic. Clinvar id is 136175.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr15-34250637-AG-C is described in CliVar as Pathogenic. Clinvar id is 136175.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr15-34250637-AG-C is described in CliVar as Pathogenic. Clinvar id is 136175.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr15-34250637-AG-C is described in CliVar as Pathogenic. Clinvar id is 136175.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr15-34250637-AG-C is described in CliVar as Pathogenic. Clinvar id is 136175.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr15-34250637-AG-C is described in CliVar as Pathogenic. Clinvar id is 136175.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr15-34250637-AG-C is described in CliVar as Pathogenic. Clinvar id is 136175.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| SLC12A6 | NM_001365088.1 | c.1584_1585delCTinsG | p.Phe529LeufsTer4 | frameshift_variant, missense_variant | Exon 12 of 26 | ENST00000354181.8 | NP_001352017.1 |
Ensembl
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1Other:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Agenesis of the corpus callosum with peripheral neuropathy Pathogenic:1Other:1
Nov 01, 2002
OMIM
Significance:Pathogenic
Review Status:no assertion criteria provided
Collection Method:literature only
- -
-
GeneReviews
Significance:not provided
Review Status:no classification provided
Collection Method:literature only
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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