rs1357953426
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Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 2P and 9B. PM2BP4_ModerateBP6_ModerateBP7BS1
The NM_020708.5(SLC12A5):c.1203C>T(p.Thr401=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000682 in 1,613,964 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000068 ( 0 hom. )
Consequence
SLC12A5
NM_020708.5 synonymous
NM_020708.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.17
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 -7 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.37).
BP6
?
Variant 20-46043289-C-T is Benign according to our data. Variant chr20-46043289-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 542331.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=-1.17 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00000684 (10/1461844) while in subpopulation MID AF= 0.000867 (5/5768). AF 95% confidence interval is 0.000341. There are 0 homozygotes in gnomad4_exome. There are 5 alleles in male gnomad4_exome subpopulation. Median coverage is 32. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC12A5 | NM_020708.5 | c.1203C>T | p.Thr401= | synonymous_variant | 9/26 | ENST00000243964.7 | |
SLC12A5 | NM_001134771.2 | c.1272C>T | p.Thr424= | synonymous_variant | 9/26 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC12A5 | ENST00000243964.7 | c.1203C>T | p.Thr401= | synonymous_variant | 9/26 | 1 | NM_020708.5 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152120Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 0.00000684 AC: 10AN: 1461844Hom.: 0 Cov.: 32 AF XY: 0.00000688 AC XY: 5AN XY: 727228
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GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152120Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74306
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Developmental and epileptic encephalopathy, 34 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Mar 19, 2023 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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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