chr20-46043920-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 3P and 3B. PM2PP2BP4_ModerateBS1_Supporting
The NM_020708.5(SLC12A5):c.1381G>A(p.Val461Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0000604 in 1,606,146 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 Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. V461V) 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.1381G>A | p.Val461Ile | missense_variant | 11/26 | ENST00000243964.7 | |
SLC12A5 | NM_001134771.2 | c.1450G>A | p.Val484Ile | missense_variant | 11/26 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC12A5 | ENST00000243964.7 | c.1381G>A | p.Val461Ile | missense_variant | 11/26 | 1 | NM_020708.5 | A1 |
Frequencies
GnomAD3 genomes AF: 0.0000658 AC: 10AN: 151944Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000494 AC: 12AN: 242886Hom.: 0 AF XY: 0.0000535 AC XY: 7AN XY: 130960
GnomAD4 exome AF: 0.0000598 AC: 87AN: 1454084Hom.: 0 Cov.: 34 AF XY: 0.0000512 AC XY: 37AN XY: 722724
GnomAD4 genome AF: 0.0000658 AC: 10AN: 152062Hom.: 0 Cov.: 32 AF XY: 0.0000807 AC XY: 6AN XY: 74332
ClinVar
Submissions by phenotype
Developmental and epileptic encephalopathy, 34 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 01, 2022 | This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 461 of the SLC12A5 protein (p.Val461Ile). This variant is present in population databases (rs201487205, 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: 576593). 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. 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. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | AiLife Diagnostics, AiLife Diagnostics | Jun 04, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at