rs35981087
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Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2
The NM_020708.5(SLC12A5):c.2403C>T(p.Gly801=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000725 in 1,613,432 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0041 ( 3 hom., cov: 33)
Exomes 𝑓: 0.00038 ( 5 hom. )
Consequence
SLC12A5
NM_020708.5 synonymous
NM_020708.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.440
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 Benign. Variant got -15 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.53).
BP6
?
Variant 20-46052982-C-T is Benign according to our data. Variant chr20-46052982-C-T is described in ClinVar as [Benign]. Clinvar id is 475650.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=-0.44 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00407 (619/152234) while in subpopulation AFR AF= 0.0142 (592/41552). AF 95% confidence interval is 0.0133. There are 3 homozygotes in gnomad4. There are 283 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 3 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC12A5 | NM_020708.5 | c.2403C>T | p.Gly801= | synonymous_variant | 19/26 | ENST00000243964.7 | |
SLC12A5 | NM_001134771.2 | c.2472C>T | p.Gly824= | synonymous_variant | 19/26 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC12A5 | ENST00000243964.7 | c.2403C>T | p.Gly801= | synonymous_variant | 19/26 | 1 | NM_020708.5 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.00405 AC: 616AN: 152116Hom.: 3 Cov.: 33
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GnomAD3 exomes AF: 0.00100 AC: 252AN: 251106Hom.: 3 AF XY: 0.000744 AC XY: 101AN XY: 135698
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GnomAD4 exome AF: 0.000377 AC: 551AN: 1461198Hom.: 5 Cov.: 31 AF XY: 0.000334 AC XY: 243AN XY: 726784
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GnomAD4 genome ? AF: 0.00407 AC: 619AN: 152234Hom.: 3 Cov.: 33 AF XY: 0.00380 AC XY: 283AN XY: 74440
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Developmental and epileptic encephalopathy, 34 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 27, 2024 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at