rs768514327
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PVS1_StrongPM2PP5_Moderate
The NM_001365088.1(SLC12A6):c.3337C>T(p.Arg1113Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,638 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
SLC12A6
NM_001365088.1 stop_gained
NM_001365088.1 stop_gained
Scores
2
2
3
Clinical Significance
Conservation
PhyloP100: 0.812
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
PVS1
?
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most 50 bp of the penultimate exon, not predicted to undergo nonsense mediated mRNA decay. There are 4 pathogenic variants in the truncated region.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 15-34235205-G-A is Pathogenic according to our data. Variant chr15-34235205-G-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 554561.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC12A6 | NM_001365088.1 | c.3337C>T | p.Arg1113Ter | stop_gained | 25/26 | ENST00000354181.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC12A6 | ENST00000354181.8 | c.3337C>T | p.Arg1113Ter | stop_gained | 25/26 | 1 | NM_001365088.1 | A1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
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GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251462Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135906
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GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461638Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2AN XY: 727154
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GnomAD4 genome ? Cov.: 32
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ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Agenesis of the corpus callosum with peripheral neuropathy Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Counsyl | Oct 25, 2017 | - - |
Computational scores
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Name
Calibrated prediction
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BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
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Dann
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Eigen_PC
Benign
FATHMM_MKL
Benign
N
MutationTaster
Benign
D;D;D;D;D;D;D;D;D;D
Vest4
GERP RS
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_DL_spliceai
Position offset: -24
Find out detailed SpliceAI scores and Pangolin per-transcript scores at