rs778801242
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 3P and 3B. PM2PP2BP4_ModerateBS1_Supporting
The NM_020708.5(SLC12A5):c.1099G>A(p.Val367Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000026 in 1,613,792 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. V367V) has been classified as Likely benign.
Frequency
Consequence
NM_020708.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC12A5 | NM_020708.5 | c.1099G>A | p.Val367Met | missense_variant | 9/26 | ENST00000243964.7 | |
SLC12A5 | NM_001134771.2 | c.1168G>A | p.Val390Met | missense_variant | 9/26 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC12A5 | ENST00000243964.7 | c.1099G>A | p.Val367Met | missense_variant | 9/26 | 1 | NM_020708.5 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000395 AC: 6AN: 151964Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000239 AC: 6AN: 251316Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135840
GnomAD4 exome AF: 0.0000246 AC: 36AN: 1461828Hom.: 0 Cov.: 31 AF XY: 0.0000248 AC XY: 18AN XY: 727234
GnomAD4 genome ? AF: 0.0000395 AC: 6AN: 151964Hom.: 0 Cov.: 31 AF XY: 0.0000539 AC XY: 4AN XY: 74218
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 13, 2021 | The c.1168G>A (p.V390M) alteration is located in exon 9 (coding exon 9) of the SLC12A5 gene. This alteration results from a G to A substitution at nucleotide position 1168, causing the valine (V) at amino acid position 390 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Epilepsy, idiopathic generalized, susceptibility to, 14;C4225257:Developmental and epileptic encephalopathy, 34 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | New York Genome Center | Feb 19, 2021 | - - |
Developmental and epileptic encephalopathy, 34 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 02, 2024 | This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 367 of the SLC12A5 protein (p.Val367Met). This variant is present in population databases (rs778801242, gnomAD 0.009%). This variant has not been reported in the literature in individuals affected with SLC12A5-related conditions. ClinVar contains an entry for this variant (Variation ID: 542317). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt SLC12A5 protein function with a negative predictive value of 80%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at