20-64048381-G-T
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4
The NM_018419.3(SOX18):c.940C>A(p.Pro314Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000454 in 1,563,578 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P314S) has been classified as Uncertain significance.
Frequency
Consequence
NM_018419.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SOX18 | NM_018419.3 | c.940C>A | p.Pro314Thr | missense_variant | 2/2 | ENST00000340356.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SOX18 | ENST00000340356.9 | c.940C>A | p.Pro314Thr | missense_variant | 2/2 | 1 | NM_018419.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000132 AC: 2AN: 151884Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000187 AC: 3AN: 160382Hom.: 0 AF XY: 0.0000339 AC XY: 3AN XY: 88516
GnomAD4 exome AF: 0.0000489 AC: 69AN: 1411694Hom.: 0 Cov.: 31 AF XY: 0.0000458 AC XY: 32AN XY: 698886
GnomAD4 genome ? AF: 0.0000132 AC: 2AN: 151884Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74168
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 17, 2023 | This sequence change replaces proline, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 314 of the SOX18 protein (p.Pro314Thr). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with SOX18-related conditions. 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 SOX18 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at