20-46022977-A-AGGAG
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 8P and 6B. PVS1BP6_ModerateBS1
The ENST00000626701.1(SLC12A5):c.257_258insGAGG(p.Gly87ArgfsTer98) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: 𝑓 0.0045 ( 0 hom., cov: 30)
Exomes 𝑓: 0.00013 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
SLC12A5
ENST00000626701.1 frameshift
ENST00000626701.1 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.00
Genes affected
SLC12A5 (HGNC:13818): (solute carrier family 12 member 5) K-Cl cotransporters are proteins that lower intracellular chloride concentrations below the electrochemical equilibrium potential. The protein encoded by this gene is an integral membrane K-Cl cotransporter that can function in either a net efflux or influx pathway, depending on the chemical concentration gradients of potassium and chloride. The encoded protein can act as a homomultimer, or as a heteromultimer with other K-Cl cotransporters, to maintain chloride homeostasis in neurons. Alternative splicing results in two transcript variants encoding different isoforms. [provided by RefSeq, Sep 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
BP6
Variant 20-46022977-A-AGGAG is Benign according to our data. Variant chr20-46022977-A-AGGAG is described in ClinVar as [Benign]. Clinvar id is 1686327.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.000129 (22/170726) while in subpopulation AFR AF= 0.00163 (9/5512). AF 95% confidence interval is 0.000851. There are 0 homozygotes in gnomad4_exome. There are 14 alleles in male gnomad4_exome subpopulation. Median coverage is 0. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SLC12A5 | NM_001134771.2 | c.121+1092_121+1093insGAGG | intron_variant | NP_001128243.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SLC12A5 | ENST00000413737.2 | c.97_98insGAGG | p.Gly34ArgfsTer98 | frameshift_variant | 2/3 | 3 | ENSP00000487291 | |||
SLC12A5 | ENST00000626701.1 | c.257_258insGAGG | p.Gly87ArgfsTer98 | frameshift_variant | 2/3 | 3 | ENSP00000487372 | |||
SLC12A5 | ENST00000454036.6 | c.121+1092_121+1093insGAGG | intron_variant | 5 | ENSP00000387694 | P3 |
Frequencies
GnomAD3 genomes AF: 0.00 AC: 363AN: 80976Hom.: 0 Cov.: 30 FAILED QC
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GnomAD4 exome AF: 0.000129 AC: 22AN: 170726Hom.: 0 Cov.: 0 AF XY: 0.000160 AC XY: 14AN XY: 87670
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GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00451 AC: 365AN: 80994Hom.: 0 Cov.: 30 AF XY: 0.00439 AC XY: 170AN XY: 38706
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Data not reliable, filtered out with message: AS_VQSR
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Mendelics | May 04, 2022 | - - |
Computational scores
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Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.